The Role of NF-κB in Myocardial Ischemia/Reperfusion Injury

Peiliang      Dong; Kemeng      Liu; Hua      Han
Abstract

Acute myocardial infarction (AMI) is a threat to human life and physical health worldwide. Timely reperfusion is very important to limit infarct size and protect ischemic myocardium. Unfortunately, it has also caused severer myocardial damage, which is called “myocardial ischemia/ reperfusion injury (MIRI)”. There is no effective clinical treatment for it. Over the past two decades, biological studies of NF-κB have improved the understanding of MIRI. Nuclear Factor-κB (NF-κB) is a major transcription factor associated with cardiovascular health and disease. It is involved in the release of pro-inflammatory factors and apoptosis of cardiomyocytes. Recent studies have shown that inhibition of NF-κB plays a protective role in acute hypoxia and reperfusion injury. Here we review the molecular regulation of NF-κB in MIRI, better understanding of NF-κB signaling mechanisms related to inflammation and crosstalk with endogenous small molecules. We hope this review will aid in improving therapeutic approaches to clinical diagnosing. This review provides evidence for the role of NF-κB in MIRI and supports its use as a therapeutic target.
Keywords: Nuclear Factor-κB, myocardial ischemia reperfusion injury, inflammation, hypoxia, endogenous protection, therapeutic target.
Graphical Abstract

[1]
Lindsey, M.L.; Bolli, R.; Canty, J.M., Jr; Du, X.J.; Frangogiannis, N.G.; Frantz, S.; Gourdie, R.G.; Holmes, J.W.; Jones, S.P.; Kloner, R.A.; Lefer, D.J.; Liao, R.; Murphy, E.; Ping, P.; Przyklenk, K.; Recchia, F.A.; Schwartz Longacre, L.; Ripplinger, C.M.; Van Eyk, J.E.; Heusch, G. Guidelines for experimental models of myocardial ischemia and infarction. Am. J. Physiol. Heart Circ. Physiol.,  2018, 314(4), H812-H838.
 [http://dx.doi.org/10.1152/ajpheart.00335.2017] [PMID:  29351451]

[2]
Mensah, G.A.; Roth, G.A.; Fuster, V. The global burden of cardiovascular diseases and risk factors: 2020 and beyond. J. Am. Coll. Cardiol.,  2019, 74(20), 2529-2532.
 [http://dx.doi.org/10.1016/j.jacc.2019.10.009] [PMID:  31727292]

[3]
Lu, L.; Ma, J.; Tang, J.; Liu, Y.; Zheng, Q.; Chen, S.; Gao, E.; Ren, J.; Yang, L.; Yang, J. Irisin attenuates myocardial ischemia/reperfusion-induced cardiac dysfunction by regulating ER-mitochondria interaction through a mitochondrial ubiquitin ligase-dependent mechanism. Clin. Transl. Med.,  2020, 10(5), e166.
 [http://dx.doi.org/10.1002/ctm2.166] [PMID:  32997406]

[4]
Blankenship, J.C.; Skelding, K.A.; Scott, T.D.; Berger, P.B.; Parise, H.; Brodie, B.R.; Witzenbichler, B.; Gaugliumi, G.; Peruga, J.Z.; Lan-sky, A.J.; Mehran, R.; Stone, G.W. Predictors of reperfusion delay in patients with acute myocardial infarction undergoing primary percu-taneous coronary intervention from the HORIZONS-AMI trial. Am. J. Cardiol.,  2010, 106(11), 1527-1533.
 [http://dx.doi.org/10.1016/j.amjcard.2010.07.033] [PMID:  21094350]

[5]
Koeppen, M.; Lee, J.W.; Seo, S.W.; Brodsky, K.S.; Kreth, S.; Yang, I.V.; Buttrick, P.M.; Eckle, T.; Eltzschig, H.K. Hypoxia-inducible fac-tor 2-alpha-dependent induction of amphiregulin dampens myocardial ischemia-reperfusion injury. Nat. Commun.,  2018, 9(1), 816.
 [http://dx.doi.org/10.1038/s41467-018-03105-2] [PMID:  29483579]

[6]
Ibáñez, B.; Heusch, G.; Ovize, M.; Van de Werf, F. Evolving therapies for myocardial ischemia/reperfusion injury. J. Am. Coll. Cardiol.,  2015, 65(14), 1454-1471.
 [http://dx.doi.org/10.1016/j.jacc.2015.02.032] [PMID:  25857912]

[7]
Algoet, M.; Janssens, S.; Himmelreich, U.; Gsell, W.; Pusovnik, M. M.; Van den E.J.; Oosterlinck, W. Myocardial ischemiareperfusion injury and the influence of inflammation. Trends Cardiovasc. Med.,  2022, 1050-1738(22), 29.
 [http://dx.doi.org/10.1016/j.tcm.2022.02.005]

[8]
Fröhlich, G.M.; Meier, P.; White, S.K.; Yellon, D.M.; Hausenloy, D.J. Myocardial reperfusion injury: Looking beyond primary PCI. Eur. Heart J.,  2013, 34(23), 1714-1722.
 [http://dx.doi.org/10.1093/eurheartj/eht090] [PMID:  23536610]

[9]
Zheng, Y.; Wan, G.; Yang, B.; Gu, X.; Lin, J. Cardioprotective natural compound pinocembrin attenuates acute ischemic myocardial injury via enhancing glycolysis. Oxid. Med. Cell. Longev.,  2020, 2020, 4850328.
 [http://dx.doi.org/10.1155/2020/4850328] [PMID:  33178386]

[10]
Cheng, Y.; Cheng, L.; Gao, X.; Chen, S.; Wu, P.; Wang, C.; Liu, Z. Covalent modification of Keap1 at Cys77 and Cys434 by pubesceno-side a suppresses oxidative stress-induced NLRP3 inflammasome activation in myocardial ischemia-reperfusion injury. Theranostics,  2021, 11(2), 861-877.
 [http://dx.doi.org/10.7150/thno.48436] [PMID:  33391509]

[11]
Fuster, J.J.; Walsh, K. Somatic mutations and clonal hematopoiesis: Unexpected potential new drivers of age-related cardiovascular dis-ease. Circ. Res.,  2018, 122(3), 523-532.
 [http://dx.doi.org/10.1161/CIRCRESAHA.117.312115] [PMID:  29420212]

[12]
Virani, S.S.; Alonso, A.; Aparicio, H.J.; Benjamin, E.J.; Bittencourt, M.S.; Callaway, C.W.; Carson, A.P.; Chamberlain, A.M.; Cheng, S.; Delling, F.N.; Elkind, M.S.V.; Evenson, K.R.; Ferguson, J.F.; Gupta, D.K.; Khan, S.S.; Kissela, B.M.; Knutson, K.L.; Lee, C.D.; Lewis, T.T.; Liu, J.; Loop, M.S.; Lutsey, P.L.; Ma, J.; Mackey, J.; Martin, S.S.; Matchar, D.B.; Mussolino, M.E.; Navaneethan, S.D.; Perak, A.M.; Roth, G.A.; Samad, Z.; Satou, G.M.; Schroeder, E.B.; Shah, S.H.; Shay, C.M.; Stokes, A.; VanWagner, L.B.; Wang, N.Y.; Tsao, C.W. Heart disease and stroke statistics-2021 update: A report from the American heart association. Circulation,  2021, 143(8), e254-e743.
 [http://dx.doi.org/10.1161/CIR.0000000000000950] [PMID:  33501848]

[13]
Davidson, S.M.; Ferdinandy, P.; Andreadou, I.; Bøtker, H.E.; Heusch, G.; Ibáñez, B.; Ovize, M.; Schulz, R.; Yellon, D.M.; Hausenloy, D.J.; Garcia-Dorado, D. Multitarget strategies to reduce myocardial ischemia/reperfusion injury: JACC review topic of the week. J. Am. Coll. Cardiol.,  2019, 73(1), 89-99.
 [http://dx.doi.org/10.1016/j.jacc.2018.09.086] [PMID:  30621955]

[14]
Heusch, G. Critical issues for the translation of cardioprotection. Circ. Res.,  2017, 120(9), 1477-1486.
 [http://dx.doi.org/10.1161/CIRCRESAHA.117.310820] [PMID:  28450365]

[15]
Heusch, G. Cardioprotection research must leave its comfort zone. Eur. Heart J.,  2018, 39(36), 3393-3395.
 [http://dx.doi.org/10.1093/eurheartj/ehy253] [PMID:  29722801]

[16]
Kelm, N.Q.; Beare, J.E.; LeBlanc, A.J. Evaluation of coronary flow reserve after myocardial ischemia reperfusion in rats. J. Vis. Exp.,  2019, (148), 10.3791-59406.
 [http://dx.doi.org/10.3791/59406]

[17]
Hausenloy, D.J.; Yellon, D.M. Myocardial ischemia-reperfusion injury: A neglected therapeutic target. J. Clin. Invest.,  2013, 123(1), 92-100.
 [http://dx.doi.org/10.1172/JCI62874] [PMID:  23281415]

[18]
Lejay, A.; Fang, F.; John, R. Ischemia reperfusion injury, ischemic conditioning and diabetes mellitus. J. Mol. Cell. Cardiol.,  2016, 91, 11-22.

[19]
Zhang, Q.; Lenardo, M.J.; Baltimore, D. 30 Years of NF-kappaB: A blossomingof relevance to human pathobiology. Cell,  2017, 168(1-2), 37-57.
 [http://dx.doi.org/10.1016/j.cell.2016.12.012] [PMID:  28086098]

[20]
Mulero, M.C.; Wang, V.Y.; Huxford, T.; Ghosh, G. Genome reading by the NF-κB transcription factors. Nucleic Acids Res.,  2019, 47(19), 9967-9989.
 [http://dx.doi.org/10.1093/nar/gkz739] [PMID:  31501881]

[21]
Sen, R.; Baltimore, D. Multiple nuclear factors interact with the immunoglobulin enhancer sequences. Cell,  1986, 46(5), 705-716.
 [http://dx.doi.org/10.1016/0092-8674(86)90346-6]

[22]
Gilmore, T.D. NF-kappa B, KBF1, dorsal, and related matters. Cell,  1990, 62(5), 841-843.
 [http://dx.doi.org/10.1016/0092-8674(90)90257-F] [PMID:  2203533]

[23]
Liu, T. Zhang, L.; Joo, D.; Sun, S.C. NF-κB signaling in inflammation. Signal Transduct. Target. Ther.,  2017, 2, 17023.
 [http://dx.doi.org/10.1038/sigtrans.2017.23] [PMID:  29158945]

[24]
Gilmore, T.D. Introduction to NF-kappaB: Players, pathways, perspectives. Oncogene,  2006, 25(51), 6680-6684.
 [http://dx.doi.org/10.1038/sj.onc.1209954] [PMID:  17072321]

[25]
Hoesel, B.; Schmid, J.A. The complexity of NF-κB signaling in inflammation and cancer. Mol. Cancer,  2013, 12, 86.
 [http://dx.doi.org/10.1186/1476-4598-12-86]

[26]
Oeckinghaus, A.; Ghosh, S. The NF-kappaB family of transcription factors and its regulation. Cold Spring Harb. Perspect. Biol.,  2009, 1(4), a000034.
 [http://dx.doi.org/10.1101/cshperspect.a000034] [PMID:  20066092]

[27]
Chew, C.L.; Conos, S.A.; Unal, B.; Tergaonkar, V. Noncoding RNAs: Master regulators of inflammatory signaling. Trends Mol. Med.,  2018, 24(1), 66-84.
 [http://dx.doi.org/10.1016/j.molmed.2017.11.003] [PMID:  29246760]

[28]
Hayden, M.S. Ghosh, S. NF-κB in immunobiology. Cell Res.,  2011, 21(2), 223-244.
 [http://dx.doi.org/10.1038/cr.2011.13] [PMID:  21243012]

[29]
Sun, S.C. The non-canonical NF-κB pathway in immunity and inflammation. Nat. Rev. Immunol.,  2017, 17(9), 545-558.
 [http://dx.doi.org/10.1038/nri.2017.52] [PMID:  28580957]

[30]
Hayden, M.S.; Ghosh, S. Signaling to NF-kappaB. Genes Dev.,  2004, 18(18), 2195-2224.
 [http://dx.doi.org/10.1101/gad.1228704] [PMID:  15371334]

[31]
Chen, L.F.; Greene, W.C. Shaping the nuclear action of NF-kappaB. Nat. Rev. Mol. Cell Biol.,  2004, 5(5), 392-401.
 [http://dx.doi.org/10.1038/nrm1368] [PMID:  15122352]

[32]
Ruland, J. Return to homeostasis: Downregulation of NF-κB responses. Nat. Immunol.,  2011, 12(8), 709-714.
 [http://dx.doi.org/10.1038/ni.2055]

[33]
Ghosh, S.; Hayden, M.S. New regulators of NF-kappaB in inflammation. Nat. Rev. Immunol.,  2008, 8(11), 837-848.
 [http://dx.doi.org/10.1038/nri2423] [PMID:  18927578]

[34]
Yamamoto, M.; Yamazaki, S.; Uematsu, S.; Sato, S.; Hemmi, H.; Hoshino, K.; Kaisho, T.; Kuwata, H.; Takeuchi, O.; Takeshige, K.; Saitoh, T.; Yamaoka, S.; Yamamoto, N.; Yamamoto, S.; Muta, T.; Takeda, K.; Akira, S. Regulation of Toll/IL-1-receptor-mediated gene expression by the inducible nuclear protein IkappaBzeta. Nature,  2004, 430(6996), 218-222.
 [http://dx.doi.org/10.1038/nature02738] [PMID:  15241416]

[35]
Cildir, G.; Low, K.C.; Tergaonkar, V. Noncanonical NF-κB signaling in health and disease. Trends Mol. Med.,  2016, 22(5), 414-429.

[36]
Dejardin, E. The alternative NF-kappaB pathway from biochemistry to biology: Pitfalls and promises for future drug development. Biochem. Pharmacol.,  2006, 72(9), 1161-1179.
 [http://dx.doi.org/10.1016/j.bcp.2006.08.007] [PMID:  16970925]

[37]
Beg, A.A.; Baltimore, D. An essential role for NF-kappaB in preventing TNF-alpha-induced cell death. Science,  1996, 274(5288), 782-784.

[38]
Sun, S.C. Controlling the fate of NIK: A central stage in noncanonical NF-kappaB signaling. Sci. Signal.,  2010, 3(123), pe18.
 [http://dx.doi.org/10.1126/scisignal.3123pe18] [PMID:  20501935]

[39]
Liao, G.; Zhang, M.; Harhaj, E.W.; Sun, S.C. Regulation of the NF-kappaB-inducing kinase by tumor necrosis factor receptor-associated factor 3-induced degradation. J. Biol. Chem.,  2004, 279(25), 26243-26250.
 [http://dx.doi.org/10.1074/jbc.M403286200] [PMID:  15084608]

[40]
Sanjo, H.; Zajonc, D.M.; Braden, R.; Norris, P.S.; Ware, C.F. Allosteric regulation of the ubiquitin: NIK and ubiquitin:TRAF3 E3 ligases by the lymphotoxin-beta receptor. J. Biol. Chem.,  2010, 285(22), 17148-17155.
 [http://dx.doi.org/10.1074/jbc.M110.105874] [PMID:  20348096]

[41]
Pearce, L.; Davidson, S.M.; Yellon, D.M. Does remote ischaemic conditioning reduce inflammation? A focus on innate immunity and cytokine response. Basic Res. Cardiol.,  2021, 116(1), 12.
 [http://dx.doi.org/10.1007/s00395-021-00852-0] [PMID:  33629195]

[42]
Honda, T.; He, Q.; Wang, F.; Redington, A.N. Acute and chronic remote ischemic conditioning attenuate septic cardiomyopathy, improve cardiac output, protect systemic organs, and improve mortality in a lipopolysaccharide-induced sepsis model. Basic Res. Cardiol.,  2019, 114(3), 15.
 [http://dx.doi.org/10.1007/s00395-019-0724-3] [PMID:  30838474]

[43]
Gori, T.; Lelieveld, J.; Münzel, T. Perspective: Cardiovascular disease and the Covid-19 pandemic. Basic Res. Cardiol.,  2020, 115(3), 32.
 [http://dx.doi.org/10.1007/s00395-020-0792-4] [PMID:  32277299]

[44]
Lang, J.P.; Wang, X.; Moura, F.A.; Siddiqi, H.K.; Morrow, D.A.; Bohula, E.A. A current review of COVID-19 for the cardiovascular spe-cialist. Am. Heart J.,  2020, 226, 29-44.
 [http://dx.doi.org/10.1016/j.ahj.2020.04.025] [PMID:  32497913]

[45]
Frank, A.; Bonney, M.; Bonney, S.; Weitzel, L.; Koeppen, M.; Eckle, T. Myocardial ischemia reperfusion injury: From basic science to clinical bedside. Semin. Cardiothorac. Vasc. Anesth.,  2012, 16(3), 123-132.
 [http://dx.doi.org/10.1177/1089253211436350] [PMID:  22368166]

[46]
Zhou, T.; Chuang, C.C.; Zuo, L. Molecular characterization of reactive oxygen species in myocardial ischemia-reperfusion injury. BioMed Res. Int.,  2015, 2015, 864946.
 [http://dx.doi.org/10.1155/2015/864946] [PMID:  26509170]

[47]
Qian, W.; Xiong, X.; Fang, Z.; Lu, H.; Wang, Z. Protective effect of tetramethylpyrazine on myocardial ischemia-reperfusion injury. Evid. Based Complement. Alternat. Med.,  2014, 2014, 107501.
 [http://dx.doi.org/10.1155/2014/107501] [PMID:  25152756]

[48]
Bulluck, H.; Yellon, D.M.; Hausenloy, D.J. Reducing myocardial infarct size: Challenges and future opportunities. Heart,  2016, 102(5), 341-348.
 [http://dx.doi.org/10.1136/heartjnl-2015-307855] [PMID:  26674987]

[49]
Olejarz, W Łacheta, D; Głuszko, A RAGE and TLRs as key targets for antiatherosclerotic therapy BioMed Res. Int.,  2018, 2018, 7675286.
 [http://dx.doi.org/10.1155/2018/7675286]

[50]
Krakauer, T. Inflammasomes, autophagy, and cell death: The trinity of innate host defense against intracellular bacteria. Mediators Inflamm.,  2019, 2019, 2471215.
 [http://dx.doi.org/10.1155/2019/2471215]

[51]
Ong, S.G.; Lee, W.H.; Theodorou, L.; Kodo, K.; Lim, S.Y.; Shukla, D.H.; Briston, T.; Kiriakidis, S.; Ashcroft, M.; Davidson, S.M.; Max-well, P.H.; Yellon, D.M.; Hausenloy, D.J. HIF-1 reduces ischaemia-reperfusion injury in the heart by targeting the mitochondrial permea-bility transition pore. Cardiovasc. Res.,  2014, 104(1), 24-36.
 [http://dx.doi.org/10.1093/cvr/cvu172] [PMID:  25063991]

[52]
Kalogeris, T.; Bao, Y.; Korthuis, R.J. Mitochondrial reactive oxygen species: A double edged sword in ischemia/reperfusion vs precondi-tioning. Redox Biol.,  2014, 2, 702-714.
 [http://dx.doi.org/10.1016/j.redox.2014.05.006] [PMID:  24944913]

[53]
Yu, L.; Feng, Z. The role of toll-like receptor signaling in the progression of heart failure. Mediators Inflamm.,  2018, 2018, 9874109.
 [http://dx.doi.org/10.1155/2018/9874109] [PMID:  29576748]

[54]
Chen, M.; Chen, C.; Gao, Y.; Li, D.; Huang, D.; Chen, Z.; Zhao, X.; Huang, Q.; Wu, D.; Lai, T.; Su, G.; Wu, B.; Zhou, B. Bergenin-activated SIRT1 inhibits TNF-α-induced proinflammatory response by blocking the NF-κB signaling pathway. Pulm. Pharmacol. Ther.,  2020, 62, 101921.
 [http://dx.doi.org/10.1016/j.pupt.2020.101921] [PMID:  32615160]

[55]
Pluijmert, N.J.; Atsma, D.E.; Quax, P.H.A. Post-ischemic myocardial inflammatory response: A complex and dynamic process susceptible to immunomodulatory therapies. Front. Cardiovasc. Med.,  2021, 8, 647785.
 [http://dx.doi.org/10.3389/fcvm.2021.647785]

[56]
Singh, A.K.; Fechtner, S.; Chourasia, M.; Sicalo, J.; Ahmed, S. Critical role of IL-1α in IL-1β-induced inflammatory responses: Coopera-tion with NF-κBp65 in transcriptional regulation. FASEB J.,  2019, 33(2), 2526-2536.
 [http://dx.doi.org/10.1096/fj.201801513R] [PMID:  30272996]

[57]
Toldo, S.; Marchetti, C.; Mauro, A.G.; Chojnacki, J.; Mezzaroma, E.; Carbone, S.; Zhang, S.; Van Tassell, B.; Salloum, F.N.; Abbate, A. Inhibition of the NLRP3 inflammasome limits the inflammatory injury following myocardial ischemia-reperfusion in the mouse. Int. J. Cardiol.,  2016, 209, 215-220.
 [http://dx.doi.org/10.1016/j.ijcard.2016.02.043] [PMID:  26896627]

[58]
Niu, L.; Zhao, Y.; Liu, S.; Pan, W. Silencing of long non coding RNA HRIM protects against myocardial ischemia/reperfusion injury via inhibition of NF κB signaling. Mol. Med. Rep.,  2020, 22(6), 5454-5462.
 [http://dx.doi.org/10.3892/mmr.2020.11597] [PMID:  33174008]

[59]
Kondylis, V.; Kumari, S.; Vlantis, K.; Pasparakis, M. The interplay of IKK, NF-κB and RIPK1 signaling in the regulation of cell death, tissue homeostasis and inflammation. Immunol. Rev.,  2017, 277(1), 113-127.
 [http://dx.doi.org/10.1111/imr.12550] [PMID:  28462531]

[60]
Kim, Y.S.; Kim, J.S.; Kwon, J.S.; Jeong, M.H.; Cho, J.G.; Park, J.C.; Kang, J.C.; Ahn, Y. BAY 11-7082, a nuclear factor-κB inhibitor, re-duces inflammation and apoptosis in a rat cardiac ischemia-reperfusion injury model. Int. Heart J.,  2010, 51(5), 348-353.
 [http://dx.doi.org/10.1536/ihj.51.348] [PMID:  20966608]

[61]
Ye, T.; Zhang, C.; Wu, G.; Wan, W.; Liang, J.; Liu, X.; Liu, D.; Yang, B. Pinocembrin attenuates autonomic dysfunction and atrial fibrilla-tion susceptibility via inhibition of the NF-κB/TNF-α pathway in a rat model of myocardial infarction. Int. Immunopharmacol.,  2019, 77, 105926.
 [http://dx.doi.org/10.1016/j.intimp.2019.105926] [PMID:  31704291]

[62]
Wang, S.; Yang, X. Eleutheroside E decreases oxidative stress and NF-κB activation and reprograms the metabolic response against hypox-ia-reoxygenation injury in H9c2 cells. Int. Immunopharmacol.,  2020, 84, 106513.

[63]
Qiang, Z.; Yu, W.; Yu, Y. Design and development of novel 1,3,5-triazine-procaine derivatives as protective agent against myocardial ischemia/reperfusion injury via inhibitor of nuclear factor-κB. Pharmacol.,  2019, 104(3-4), 126-138.
 [http://dx.doi.org/10.1159/000500702] [PMID:  31212291]

[64]
Poncelas, M.; Inserte, J.; Aluja, D.; Hernando, V.; Vilardosa, U.; Garcia-Dorado, D. Delayed, oral pharmacological inhibition of calpains attenuates adverse post-infarction remodelling. Cardiovasc. Res.,  2017, 113(8), 950-961.
 [http://dx.doi.org/10.1093/cvr/cvx073] [PMID:  28460013]

[65]
Heyninck, K.; Beyaert, R. Crosstalk between NF-kappaB-activating and apoptosis-inducing proteins of the TNF-receptor complex. Mol. Cell Biol. Res. Commun.,  2001, 4(5), 259-265.
 [http://dx.doi.org/10.1006/mcbr.2001.0295] [PMID:  11529675]

[66]
Attiq, A.; Jalil, J.; Husain, K.; Ahmad, W. Raging the war against inflammation with natural products. Front. Pharmacol.,  2018, 9, 976.
 [http://dx.doi.org/10.3389/fphar.2018.00976] [PMID:  30245627]

[67]
Mariappan, N.; Elks, C.M.; Sriramula, S.; Guggilam, A.; Liu, Z.; Borkhsenious, O.; Francis, J. NF-kappaB-induced oxidative stress con-tributes to mitochondrial and cardiac dysfunction in type II diabetes. Cardiovasc. Res.,  2010, 85(3), 473-483.
 [http://dx.doi.org/10.1093/cvr/cvp305] [PMID:  19729361]

[68]
Batista, M.L., Jr; Rosa, J.C.; Lopes, R.D.; Lira, F.S.; Martins, E., Jr; Yamashita, A.S.; Brum, P.C.; Lancha, A.H., Jr; Lopes, A.C.; Seelaender, M. Exercise training changes IL-10/TNF-alpha ratio in the skeletal muscle of post-MI rats. Cytokine,  2010, 49(1), 102-108.
 [http://dx.doi.org/10.1016/j.cyto.2009.10.007] [PMID:  19948415]

[69]
Shimamoto, A.; Chong, A.J.; Yada, M.; Shomura, S.; Takayama, H.; Fleisig, A.J.; Agnew, M.L.; Hampton, C.R.; Rothnie, C.L.; Spring, D.J.; Pohlman, T.H.; Shimpo, H.; Verrier, E.D. Inhibition of Toll-like receptor 4 with eritoran attenuates myocardial ischemia-reperfusion inju-ry. Circulation,  2006, 114(1)(Suppl.), I270-I274.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.105.000901] [PMID:  16820585]

[70]
Vilahur, G.; Badimon, L. Ischemia/reperfusion activates myocardial innate immune response: The key role of the toll-like receptor. Front. Physiol.,  2014, 5, 496.
 [http://dx.doi.org/10.3389/fphys.2014.00496] [PMID:  25566092]

[71]
Ve, T.; Vajjhala, P.R.; Hedger, A.; Croll, T.; DiMaio, F.; Horsefield, S.; Yu, X.; Lavrencic, P.; Hassan, Z.; Morgan, G.P.; Mansell, A.; Mobli, M.; O’Carroll, A.; Chauvin, B.; Gambin, Y.; Sierecki, E.; Landsberg, M.J.; Stacey, K.J.; Egelman, E.H.; Kobe, B. Structural basis of TIR-domain-assembly formation in MAL- and MyD88-dependent TLR4 signaling. Nat. Struct. Mol. Biol.,  2017, 24(9), 743-751.
 [http://dx.doi.org/10.1038/nsmb.3444] [PMID:  28759049]

[72]
Zhao, Y.; Xu, Y.; Zhang, J.; Ji, T. Cardioprotective effect of carvedilol: Inhibition of apoptosis in H9c2 cardiomyocytes via the TLR4/NF-κB pathway following ischemia/reperfusion injury. Exp. Ther. Med.,  2014, 8(4), 1092-1096.

[73]
Cristi-Montero, C.; Sánchez-Collado, P.; Veneroso, C.; Cuevas, M.J.; González-Gallego, J. Efecto del ejercicio agudo sobre la expresión del receptor tipo Toll-4 y los mecanismos inflamatorios en corazón de rata. Rev. Med. Chil.,  2012, 140(10), 1282-1288.
 [http://dx.doi.org/10.4067/S0034-98872012001000007] [PMID:  23559285]

[74]
Chen, M.; Li, W.; Zhang, Y.; Yang, J. MicroRNA-20a protects human aortic endothelial cells from Ox-LDL-induced inflammation through targeting TLR4 and TXNIP signaling. Biomed. Pharmacother.,  2018, 103, 191-197.
 [http://dx.doi.org/10.1016/j.biopha.2018.03.129]

[75]
Bi, Q.R.; Hou, J.J.; Qi, P. TXNIP/TRX/NF-κB and MAPK/NF-κB pathways involved in the cardiotoxicity induced by Venenum Bufonis in rats. Sci. Rep.,  2016, 6, 22759.
 [http://dx.doi.org/10.1038/srep22759]

[76]
Gordon, J.W.; Shaw, J.A. Kirshenbaum, LA Multiple facets of NF-κB in the heart: To be or not to NF-κB. Circ. Res.,  2011, 108(9), 1122-1132.

[77]
Maekawa, N.; Wada, H.; Kanda, T.; Niwa, T.; Yamada, Y.; Saito, K.; Fujiwara, H.; Sekikawa, K.; Seishima, M. Improved myocardial is-chemia/reperfusion injury in mice lacking tumor necrosis factor-alpha. J. Am. Coll. Cardiol.,  2002, 39(7), 1229-1235.
 [http://dx.doi.org/10.1016/S0735-1097(02)01738-2] [PMID:  11923051]

[78]
Zhang, X.; Du, Q.; Yang, Y. The protective effect of Luteolin on myocardial ischemia/reperfusion (I/R) injury through TLR4/NF-κB/NLRP3 inflammasome pathway. Biomed. Pharmacother.,  2017, 91, 1042-1052.

[79]
Yuan, L.; Dai, X.; Fu, H.; Sui, D.; Lin, L.; Yang, L.; Zha, P.; Wang, X.; Gong, G. Vaspin protects rats against myocardial ische-mia/reperfusion injury (MIRI) through the TLR4/NF-κB signaling pathway. Eur. J. Pharmacol.,  2018, 835, 132-139.
 [http://dx.doi.org/10.1016/j.ejphar.2018.07.052] [PMID:  30063916]

[80]
Abeyrathna, P.; Su, Y. The critical role of Akt in cardiovascular function. Vascul. Pharmacol.,  2015, 74, 38-48.
 [http://dx.doi.org/10.1016/j.vph.2015.05.008] [PMID:  26025205]

[81]
Li, Y.; Xia, J.; Jiang, N.; Xian, Y.; Ju, H.; Wei, Y.; Zhang, X. Corin protects H2O2-induced apoptosis through PI3K/AKT and NF-κB path-way in cardiomyocytes. Biomed. Pharmacother.,  2018, 97, 594-599.
 [http://dx.doi.org/10.1016/j.biopha.2017.10.090] [PMID:  29101802]

[82]
Nakayama, K.; Kataoka, N. Regulation of gene expression under hypoxic conditions. Int. J. Mol. Sci.,  2019, 20(13), 3278.
 [http://dx.doi.org/10.3390/ijms20133278] [PMID:  31277312]

[83]
Li, R.L.; He, L.Y.; Zhang, Q.; Liu, J.; Lu, F.; Duan, H.X.; Fan, L.H.; Peng, W.; Huang, Y.L.; Wu, C.J. HIF-1α is a potential molecular target for herbal medicine to treat diseases. Drug Des. Devel. Ther.,  2020, 14(14), 4915-4949.
 [http://dx.doi.org/10.2147/DDDT.S274980] [PMID:  33235435]

[84]
Sies, H.; Berndt, C.; Jones, D.P. Oxidative stress. Annu. Rev. Biochem.,  2017, 86, 715-748.
 [http://dx.doi.org/10.1146/annurev-biochem-061516-045037] [PMID:  28441057]

[85]
Qiu, Y.; Huang, X.; He, W. The regulatory role of HIF-1 in tubular epithelial cells in response to kidney injury. Histol. Histopathol.,  2020, 35(4), 321-330.
 [PMID:  31691948]

[86]
Cummins, E.P.; Berra, E.; Comerford, K.M.; Ginouves, A.; Fitzgerald, K.T.; Seeballuck, F.; Godson, C.; Nielsen, J.E.; Moynagh, P.; Pouyssegur, J.; Taylor, C.T. Prolyl hydroxylase-1 negatively regulates IkappaB kinase-beta, giving insight into hypoxia-induced NFkap-paB activity. Proc. Natl. Acad. Sci. USA,  2006, 103(48), 18154-18159.
 [http://dx.doi.org/10.1073/pnas.0602235103] [PMID:  17114296]

[87]
Belaiba, R.S.; Bonello, S.; Zähringer, C.; Schmidt, S.; Hess, J.; Kietzmann, T.; Görlach, A. Hypoxia up-regulates hypoxia-inducible factor-1alpha transcription by involving phosphatidylinositol 3-kinase and nuclear factor kappaB in pulmonary artery smooth muscle cells. Mol. Biol. Cell,  2007, 18(12), 4691-4697.
 [http://dx.doi.org/10.1091/mbc.e07-04-0391] [PMID:  17898080]

[88]
van Uden, P.; Kenneth, N.S.; Rocha, S. Regulation of hypoxia-inducible factor-1alpha by NF-kappaB. Biochem. J.,  2008, 412(3), 477-484.
 [http://dx.doi.org/10.1042/BJ20080476] [PMID:  18393939]

[89]
Han, M.; Chen, X.C.; Sun, M.H.; Gai, M.T.; Yang, Y.N.; Gao, X.M.; Ma, X.; Chen, B.D.; Ma, Y.T. Overexpression of IκBα in cardiomyo-cytes alleviates hydrogen peroxide-induced apoptosis and autophagy by inhibiting NF-κB activation. Lipids Health Dis.,  2020, 19(1), 150.
 [http://dx.doi.org/10.1186/s12944-020-01327-2] [PMID:  32580730]

[90]
Bandarra, D.; Biddlestone, J.; Mudie, S.; Müller, H.A.; Rocha, S. HIF-1α restricts NF-κB-dependent gene expression to control innate im-munity signals. Dis. Model. Mech.,  2015, 8(2), 169-181.
 [http://dx.doi.org/10.1242/dmm.017285] [PMID:  25510503]

[91]
Walmsley, S.R.; Print, C.; Farahi, N.; Peyssonnaux, C.; Johnson, R.S.; Cramer, T.; Sobolewski, A.; Condliffe, A.M.; Cowburn, A.S.; John-son, N.; Chilvers, E.R. Hypoxia-induced neutrophil survival is mediated by HIF-1α-dependent NF-kappaB activity. J. Exp. Med.,  2005, 201(1), 105-115.
 [http://dx.doi.org/10.1084/jem.20040624] [PMID:  15630139]

[92]
Rius, J.; Guma, M.; Schachtrup, C.; Akassoglou, K.; Zinkernagel, A.S.; Nizet, V.; Johnson, R.S.; Haddad, G.G.; Karin, M. NF-kappaB links innate immunity to the hypoxic response through transcriptional regulation of HIF-1alpha. Nature,  2008, 453(7196), 807-811.
 [http://dx.doi.org/10.1038/nature06905] [PMID:  18432192]

[93]
Zhou, Z.; Chen, S.; Tian, Z.; Deng, S.; Yi, X.; Yang, S.; Yang, X.; Jin, L.; Shi, W. miR-20b-5p attenuates hypoxia-induced apoptosis in cardiomyocytes via the HIF-1α/NF-κB pathway. Acta Biochim. Biophys. Sin. (Shanghai),  2020, 52(9), 927-934.
 [http://dx.doi.org/10.1093/abbs/gmaa056] [PMID:  32510153]

[94]
Lee, J.W.; Ko, J.; Ju, C.; Eltzschig, H.K. Hypoxia signaling in human diseases and therapeutic targets. Exp. Mol. Med.,  2019, 51(6), 1-13.
 [http://dx.doi.org/10.1038/s12276-019-0235-1] [PMID:  31221962]

[95]
Perrino, C.; Barabási, A.L.; Condorelli, G.; Davidson, S.M.; De Windt, L.; Dimmeler, S.; Engel, F.B.; Hausenloy, D.J.; Hill, J.A.; Van Laake, L.W.; Lecour, S.; Leor, J.; Madonna, R.; Mayr, M.; Prunier, F.; Sluijter, J.P.G.; Schulz, R.; Thum, T.; Ytrehus, K.; Ferdinandy, P. Epigenomic and transcriptomic approaches in the post-genomic era: Path to novel targets for diagnosis and therapy of the ischaemic heart? position paper of the European society of cardiology working group on cellular biology of the heart. Cardiovasc. Res.,  2017, 113(7), 725-736.
 [http://dx.doi.org/10.1093/cvr/cvx070] [PMID:  28460026]

[96]
Mayoral-González, I.; Calderón-Sánchez, E.M.; Galeano-Otero, I. Cardiac protection induced by urocortin-2 enables the regulation of apoptosis and fibrosis after ischemia and reperfusion involving miR-29a modulation. Mol. Ther. Nucleic Acids,  2022, 27, 838-853.
 [http://dx.doi.org/10.1016/j.omtn.2022.01.003]

[97]
Guo, H.; Ingolia, N.T.; Weissman, J.S.; Bartel, D.P. Mammalian microRNAs predominantly act to decrease target mRNA levels. Nature,  2010, 466(7308), 835-840.
 [http://dx.doi.org/10.1038/nature09267] [PMID:  20703300]

[98]
Ebert, M.S.; Sharp, P.A. Roles for microRNAs in conferring robustness to biological processes. Cell,  2012, 149(3), 515-524.
 [http://dx.doi.org/10.1016/j.cell.2012.04.005] [PMID:  22541426]

[99]
Mahlab-Aviv, S.; Linial, N.; Linial, M. MiRNA combinatorics and its role in cell state control-a probabilistic approach. Front. Mol. Biosci.,  2021, 8, 772852.
 [http://dx.doi.org/10.3389/fmolb.2021.772852] [PMID:  34993232]

[100]
Suofu, Y.; Wang, X.; He, Y.; Li, F.; Zhang, Y.; Carlisle, D.L.; Friedlander, R.M. Mir-155 knockout protects against ischemia/reperfusion-induced brain injury and hemorrhagic transformation. Neuroreport,  2020, 31(3), 235-239.
 [http://dx.doi.org/10.1097/WNR.0000000000001382] [PMID:  31876686]

[101]
Song, C.L.; Liu, B.; Wang, J.P.; Zhang, B.L.; Zhang, J.C.; Zhao, L.Y.; Shi, Y.F.; Li, Y.X.; Wang, G.; Diao, H.Y.; Li, Q.; Xue, X.; Wu, J.D.; Liu, J.; Yu, Y.P.; Cai, D.; Liu, Z.X. Anti-apoptotic effect of microRNA-30b in early phase of rat myocardial ischemia-reperfusion injury model. J. Cell. Biochem.,  2015, 116(11), 2610-2619.
 [http://dx.doi.org/10.1002/jcb.25208] [PMID:  25925903]

[102]
Wang, X.; Ha, T.; Liu, L.; Zou, J.; Zhang, X.; Kalbfleisch, J.; Gao, X.; Williams, D.; Li, C. Increased expression of microRNA-146a de-creases myocardial ischaemia/reperfusion injury. Cardiovasc. Res.,  2013, 97(3), 432-442.
 [http://dx.doi.org/10.1093/cvr/cvs356] [PMID:  23208587]

[103]
Li, D.; Zhou, J.; Yang, B.; Yu, Y. microRNA-340-5p inhibits hypoxia/reoxygenation-induced apoptosis and oxidative stress in cardiomy-ocytes by regulating the Act1/NF-κB pathway. J. Cell. Biochem.,  2019, 120(9), 14618-14627.
 [http://dx.doi.org/10.1002/jcb.28723] [PMID:  30989715]

[104]
Huang, P.; Yang, D.; Yu, L.; Shi, Y. Downregulation of lncRNA ZFAS1 protects H9c2 cardiomyocytes from ischemia/reperfusion induced apoptosis via the miR 590 3p/NF κB signaling pathway. Mol. Med. Rep.,  2020, 22(3), 2300-2306.
 [http://dx.doi.org/10.3892/mmr.2020.11340] [PMID:  32705215]

[105]
Zhao, D.; Shun, E.; Ling, F.; Liu, Q.; Warsi, A.; Wang, B.; Zhou, Q.; Zhu, C.; Zheng, H.; Liu, K.; Zheng, X. Plk2 regulated by miR-128 induces ischemia-reperfusion injury in cardiac cells. Mol. Ther. Nucleic Acids,  2020, 19, 458-467.
 [http://dx.doi.org/10.1016/j.omtn.2019.11.029] [PMID:  31902745]

[106]
Liu, J.Y.; Shang, J.; Mu, X.D.; Gao, Z.Y. Protective effect of down-regulated microRNA-27a mediating high thoracic epidural block on myocardial ischemia-reperfusion injury in mice through regulating ABCA1 and NF-κB signaling pathway. Biomed. Pharmacother.,  2019, 112, 108606.

[107]
Pan, Y.Q.; Li, J.; Li, X.W.; Li, Y.C.; Li, J.; Lin, J.F. Effect of miR-21/TLR4/NF-κB pathway on myocardial apoptosis in rats with myocar-dial ischemia-reperfusion. Eur. Rev. Med. Pharmacol. Sci.,  2018, 22(22), 7928-7937.

[108]
Li, Y.; Fei, L.; Wang, J.; Niu, Q. Inhibition of miR-217 protects against myocardial ischemia-reperfusion injury through inactivating NF-κB and MAPK pathways. Cardiovasc. Eng. Technol.,  2020, 11(2), 219-227.
 [http://dx.doi.org/10.1007/s13239-019-00452-z] [PMID:  31916040]

[109]
Liu, Z.; Tao, B.; Fan, S.; Pu, Y.; Xia, H.; Xu, L. MicroRNA-145 protects against myocardial ischemia reperfusion injury via CaMKII-mediated antiapoptotic and anti-inflammatory pathways. Oxid. Med. Cell. Longev.,  2019, 2019, 8948657.
 [http://dx.doi.org/10.1155/2019/8948657]

[110]
Arroyo, A.B.; de Los Reyes-García, A.M.; Rivera-Caravaca, J.M.; Valledor, P.; García-Barberá, N.; Roldán, V.; Vicente, V.; Martínez, C.; González-Conejero, R. MiR-146a regulates neutrophil extracellular trap formation that predicts adverse cardiovascular events in patients with atrial fibrillation. Arterioscler. Thromb. Vasc. Biol.,  2018, 38(4), 892-902.
 [http://dx.doi.org/10.1161/ATVBAHA.117.310597] [PMID:  29437577]

[111]
Zhang, W.; Shao, M.; He, X.; Wang, B.; Li, Y.; Guo, X. Overexpression of microRNA-146 protects against oxygen-glucose depriva-tion/recovery-induced cardiomyocyte apoptosis by inhibiting the NF-κB/TNF-α signaling pathway. Mol. Med. Rep.,  2018, 17(1), 1913-1918.
 [http://dx.doi.org/10.3892/mmr.2017.8073] [PMID:  29257202]

[112]
He, L.; Wang, Z.; Zhou, R.; Xiong, W.; Yang, Y.; Song, N.; Qian, J. Dexmedetomidine exerts cardioprotective effect through miR-146a-3p targeting IRAK1 and TRAF6 via inhibition of the NF-κB pathway. Biomed. Pharmacother.,  2021, 133, 110993.
 [http://dx.doi.org/10.1016/j.biopha.2020.110993] [PMID:  33220608]

[113]
Vicencio, J.M.; Yellon, D.M.; Sivaraman, V.; Das, D.; Boi-Doku, C.; Arjun, S.; Zheng, Y.; Riquelme, J.A.; Kearney, J.; Sharma, V.; Multhoff, G.; Hall, A.R.; Davidson, S.M. Plasma exosomes protect the myocardium from ischemia-reperfusion injury. J. Am. Coll. Cardiol.,  2015, 65(15), 1525-1536.
 [http://dx.doi.org/10.1016/j.jacc.2015.02.026] [PMID:  25881934]

[114]
Chen, L.; Wang, Y.; Pan, Y.; Zhang, L.; Shen, C.; Qin, G.; Ashraf, M.; Weintraub, N.; Ma, G.; Tang, Y. Cardiac progenitor-derived exo-somes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochem. Biophys. Res. Commun.,  2013, 431(3), 566-571.
 [http://dx.doi.org/10.1016/j.bbrc.2013.01.015] [PMID:  23318173]

[115]
Dai, Y.; Wang, S.; Chang, S.; Ren, D.; Shali, S.; Li, C.; Yang, H.; Huang, Z.; Ge, J. M2 macrophage-derived exosomes carry microRNA-148a to alleviate myocardial ischemia/reperfusion injury via inhibiting TXNIP and the TLR4/NF-κB/NLRP3 inflammasome signaling pathway. J. Mol. Cell. Cardiol.,  2020, 142, 65-79.
 [http://dx.doi.org/10.1016/j.yjmcc.2020.02.007] [PMID:  32087217]

[116]
Li, H.; Yu, B.; Li, J.; Su, L.; Yan, M.; Zhu, Z.; Liu, B. Overexpression of lncRNA H19 enhances carcinogenesis and metastasis of gastric cancer. Oncotarget,  2014, 5(8), 2318-2329.
 [http://dx.doi.org/10.18632/oncotarget.1913] [PMID:  24810858]

[117]
Wang, K.; Liu, C.Y.; Zhou, L.Y.; Wang, J.X.; Wang, M.; Zhao, B.; Zhao, W.K.; Xu, S.J.; Fan, L.H.; Zhang, X.J.; Feng, C.; Wang, C.Q.; Zhao, Y.F.; Li, P.F. APF lncRNA regulates autophagy and myocardial infarction by targeting miR-188-3p. Nat. Commun.,  2015, 6, 6779.
 [http://dx.doi.org/10.1038/ncomms7779] [PMID:  25858075]

[118]
Gomes, C.P.C.; Spencer, H.; Ford, K.L.; Michel, L.Y.M.; Baker, A.H.; Emanueli, C.; Balligand, J.L.; Devaux, Y. The function and thera-peutic potential of long non-coding RNAs in cardiovascular development and disease. Mol. Ther. Nucleic Acids,  2017, 8, 494-507.
 [http://dx.doi.org/10.1016/j.omtn.2017.07.014] [PMID:  28918050]

[119]
Liu, Y.; Li, G.; Lu, H. Expression profiling and ontology analysis of long noncoding RNAs in post-ischemic heart and their implied roles in ischemia/reperfusion injury. Gene,  2014, 543(1), 15-21.

[120]
Boon, R.A.; Jaé, N.; Holdt, L.; Dimmeler, S. Long noncoding RNAs: From clinical genetics to therapeutic targets? J. Am. Coll. Cardiol.,  2016, 67(10), 1214-1226.
 [http://dx.doi.org/10.1016/j.jacc.2015.12.051] [PMID:  26965544]

[121]
Kreutzer, F.P.; Fiedler, J.; Thum, T. Non-coding RNAs: Key players in cardiac disease. J. Physiol.,  2020, 598(14), 2995-3003.
 [http://dx.doi.org/10.1113/JP278131] [PMID:  31291008]

[122]
Ke, S.; Li, R.C.; Meng, F.K.; Fang, M.H. NKILA inhibits NF-κB signaling and suppresses tumor metastasis. Aging (Albany NY),  2018, 10(1), 56-71.
 [http://dx.doi.org/10.18632/aging.101359] [PMID:  29348395]

[123]
Liu, Q.; Liu, Z.; Zhou, L.J.; Cui, Y.L.; Xu, J.M. The long noncoding RNA NKILA protects against myocardial ischaemic injury by enhanc-ing myocardin expression via suppressing the NF-κB signalling pathway. Exp. Cell Res.,  2020, 387(2), 111774.
 [http://dx.doi.org/10.1016/j.yexcr.2019.111774] [PMID:  31838061]

[124]
Wang, D.; Chang, P.S.; Wang, Z.; Sutherland, L.; Richardson, J.A.; Small, E.; Krieg, P.A.; Olson, E.N. Activation of cardiac gene expres-sion by myocardin, a transcriptional cofactor for serum response factor. Cell,  2001, 105(7), 851-862.
 [http://dx.doi.org/10.1016/S0092-8674(01)00404-4] [PMID:  11439182]

[125]
Wang, Z.; Wang, D.Z.; Pipes, G.C.; Olson, E.N. Myocardin is a master regulator of smooth muscle gene expression. Proc. Natl. Acad. Sci. USA,  2003, 100(12), 7129-7134.
 [http://dx.doi.org/10.1073/pnas.1232341100] [PMID:  12756293]

[126]
Huang, J.; Min, Lu M.; Cheng, L.; Yuan, L.J.; Zhu, X.; Stout, A.L.; Chen, M.; Li, J.; Parmacek, M.S. Myocardin is required for cardiomyo-cyte survival and maintenance of heart function. Proc. Natl. Acad. Sci. USA,  2009, 106(44), 18734-18739.
 [http://dx.doi.org/10.1073/pnas.0910749106] [PMID:  19850880]

[127]
Liao, X.H. Wang, N.; Zhao, D.W.; Zheng, D.L.; Zheng, L.; Xing, W.J.; Zhou, H.; Cao, D.S.; Zhang, T.C. NF-κB (p65) negatively regulates myocardin-induced cardiomyocyte hypertrophy through multiple mechanisms. Cell. Signal.,  2014, 26(12), 2738-2748.
 [http://dx.doi.org/10.1016/j.cellsig.2014.08.006] [PMID:  25152367]

[128]
D’Onofrio, N.; Servillo, L.; Balestrieri, M.L. SIRT1 and SIRT6 signaling pathways in cardiovascular disease protection. Antioxid. Redox Signal.,  2018, 28(8), 711-732.
 [http://dx.doi.org/10.1089/ars.2017.7178] [PMID:  28661724]

[129]
Yang, Y.; Duan, W.; Li, Y.; Jin, Z.; Yan, J.; Yu, S.; Yi, D. Novel role of silent information regulator 1 in myocardial ischemia. Circulation,  2013, 128(20), 2232-2240.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.113.002480] [PMID:  24218438]

[130]
Potenza, M.A.; Sgarra, L.; Nacci, C.; Leo, V.; De Salvia, M.A.; Montagnani, M. Activation of AMPK/SIRT1 axis is required for adiponec-tin-mediated preconditioning on myocardial ischemia-reperfusion (I/R) injury in rats. PLoS One,  2019, 14(1), e0210654.
 [http://dx.doi.org/10.1371/journal.pone.0210654] [PMID:  30653603]

[131]
Ding, M.; Lei, J.; Han, H.; Li, W.; Qu, Y.; Fu, E.; Fu, F.; Wang, X. SIRT1 protects against myocardial ischemia-reperfusion injury via acti-vating eNOS in diabetic rats. Cardiovasc. Diabetol.,  2015, 14, 143.
 [http://dx.doi.org/10.1186/s12933-015-0299-8] [PMID:  26489513]

[132]
Xu, F.; Xu, J.; Xiong, X.; Deng, Y. Salidroside inhibits MAPK, NF-κB, and STAT3 pathways in psoriasis-associated oxidative stress via SIRT1 activation. Redox Rep.,  2019, 24(1), 70-74.
 [http://dx.doi.org/10.1080/13510002.2019.1658377] [PMID:  31495284]

[133]
Yang, H.; Zhang, W.; Pan, H.; Feldser, H.G.; Lainez, E.; Miller, C.; Leung, S.; Zhong, Z.; Zhao, H.; Sweitzer, S.; Considine, T.; Riera, T.; Suri, V.; White, B.; Ellis, J.L.; Vlasuk, G.P.; Loh, C. SIRT1 activators suppress inflammatory responses through promotion of p65 deacetylation and inhibition of NF-κB activity. PLoS One,  2012, 7(9), e46364.
 [http://dx.doi.org/10.1371/journal.pone.0046364] [PMID:  23029496]

[134]
Li, D.; Wang, X.; Huang, Q.; Li, S.; Zhou, Y.; Li, Z. Cardioprotection of CAPE-oNO2 against myocardial ischemia/reperfusion induced ROS generation via regulating the SIRT1/eNOS/NF-κB pathway in vivo and in vitro. Redox Biol.,  2018, 15, 62-73.
 [http://dx.doi.org/10.1016/j.redox.2017.11.023] [PMID:  29220696]

[135]
Benjamin, E.J.; Virani, S.S.; Callaway, C.W.; Chamberlain, A.M.; Chang, A.R.; Cheng, S.; Chiuve, S.E.; Cushman, M.; Delling, F.N.; Deo, R.; de Ferranti, S.D.; Ferguson, J.F.; Fornage, M.; Gillespie, C.; Isasi, C.R.; Jiménez, M.C.; Jordan, L.C.; Judd, S.E.; Lackland, D.; Licht-man, J.H.; Lisabeth, L.; Liu, S.; Longenecker, C.T.; Lutsey, P.L.; Mackey, J.S.; Matchar, D.B.; Matsushita, K.; Mussolino, M.E.; Nasir, K.; O’Flaherty, M.; Palaniappan, L.P.; Pandey, A.; Pandey, D.K.; Reeves, M.J.; Ritchey, M.D.; Rodriguez, C.J.; Roth, G.A.; Rosamond, W.D.; Sampson, U.K.A.; Satou, G.M.; Shah, S.H.; Spartano, N.L.; Tirschwell, D.L.; Tsao, C.W.; Voeks, J.H.; Willey, J.Z.; Wilkins, J.T.; Wu, J.H.; Alger, H.M.; Wong, S.S.; Muntner, P. Heart disease and stroke statistics-2018 update: A report from the American heart association. Circulation,  2018, 137(12), e67-e492.
 [http://dx.doi.org/10.1161/CIR.0000000000000558] [PMID:  29386200]

[136]
Paradies, G.; Paradies, V.; Ruggiero, F.M.; Petrosillo, G. Mitochondrial bioenergetics and cardiolipin alterations in myocardial ischemia-reperfusion injury: Implications for pharmacological cardioprotection. Am. J. Physiol. Heart Circ. Physiol.,  2018, 315(5), H1341-H1352.
 [http://dx.doi.org/10.1152/ajpheart.00028.2018] [PMID:  30095969]

[137]
Wu, Y.; Liu, H.; Wang, X. Cardioprotection of pharmacological postconditioning on myocardial ischemia/reperfusion injury. Life Sci.,  2021, 264, 118628.
 [http://dx.doi.org/10.1016/j.lfs.2020.118628] [PMID:  33131670]

[138]
Zhang, J.; Zhang, J.; Yu, P.; Chen, M.; Peng, Q.; Wang, Z.; Dong, N. Remote ischaemic preconditioning and sevoflurane postconditioning synergistically protect rats from myocardial injury induced by ischemia and reperfusion partly via inhibition TLR4/MyD88/NF-κB signal-ing pathway. Cell. Physiol. Biochem.,  2017, 41(1), 22-32.
 [http://dx.doi.org/10.1159/000455815] [PMID:  28135708]

[139]
Stein, A.B.; Bolli, R.; Dawn, B. Carbon monoxide induces a late preconditioning-mimetic cardioprotective and antiapoptotic milieu in the myocardium. J. Mol. Cell. Cardiol.,  2012, 52(1), 228-236.

[140]
Luo, C.; Yang, H.; Tang, C.; Yao, G.; Kong, L.; He, H.; Zhou, Y. Kaempferol alleviates insulin resistance via hepatic IKK/NF-κB signal in type 2 diabetic rats. Int. Immunopharmacol.,  2015, 28(1), 744-750.
 [http://dx.doi.org/10.1016/j.intimp.2015.07.018] [PMID:  26263168]

[141]
Zhang, J.; Chen, Y.; Luo, H. Recent update on the pharmacological effects and mechanisms of dihydromyricetin. Front. Pharmacol.,  2018, 9, 1204.
 [http://dx.doi.org/10.3389/fphar.2018.01204]

[142]
Xu, X.N.; Jiang, Y. Yan, LY Aesculin suppresses the NLRP3 inflammasome-mediated pyroptosis via the Akt/GSK3β/NF-κB pathway to mitigate myocardial ischemia/reperfusion injury. Phytomedicine,  2021, 92, 153687.

[143]
Wang, Z.K.; Chen, R.R.; Li, J.H. Puerarin protects against myocardial ischemia/reperfusion injury by inhibiting inflammation and the NLRP3 inflammasome: The role of the SIRT1/NF-κB pathway. Int. Immunopharmacol.,  2020, 89(B), 107086.
 [http://dx.doi.org/10.1016/j.intimp.2020.107086]

[144]
Luan, Y.; Sun, C.; Wang, J.; Jiang, W.; Xin, Q.; Zhang, Z.; Wang, Y. Baicalin attenuates myocardial ischemia-reperfusion injury through Akt/NF-κB pathway. J. Cell. Biochem.,  2019, 120(3), 3212-3219.
 [http://dx.doi.org/10.1002/jcb.27587] [PMID:  30242878]

[145]
Wu, W.Y.; Wang, W.Y.; Ma, Y.L.; Yan, H.; Wang, X.B.; Qin, Y.L.; Su, M.; Chen, T.; Wang, Y.P. Sodium tanshinone IIA silate inhibits oxygen-glucose deprivation/recovery-induced cardiomyocyte apoptosis via suppression of the NF-κB/TNF-α pathway. Br. J. Pharmacol.,  2013, 169(5), 1058-1071.
 [http://dx.doi.org/10.1111/bph.12185] [PMID:  23517194]

[146]
Dong, L.Y.; Chen, F.; Xu, M.; Yao, L.P.; Zhang, Y.J.; Zhuang, Y. Quercetin attenuates myocardial ischemia-reperfusion injury via down-regulation of the HMGB1-TLR4-NF-κB signaling pathway. Am. J. Transl. Res.,  2018, 10(5), 1273-1283.
 [PMID:  29887944]

[147]
Zhang, Y.; Shi, K.; Lin, T.; Xia, F.; Cai, Y.; Ye, Y.; Liu, L.; Liu, F. Ganoderic acid A alleviates myocardial ischemia-reperfusion injury in rats by regulating JAK2/STAT3/NF-κB pathway. Int. Immunopharmacol.,  2020, 84, 106543.
 [http://dx.doi.org/10.1016/j.intimp.2020.106543] [PMID:  32353688]

[148]
Zhao, L.; Zhou, Z.; Zhu, C.; Fu, Z.; Yu, D. Luteolin alleviates myocardial ischemia reperfusion injury in rats via Siti1/NLRP3/NF-κB pathway. Int. Immunopharmacol.,  2020, 85, 106680.
 [http://dx.doi.org/10.1016/j.intimp.2020.106680] [PMID:  32544871]

[149]
Li, T.; Yu, J.; Chen, R.; Wu, J.; Fei, J.; Bo, Q.; Xue, L.; Li, D. Mycophenolate mofetil attenuates myocardial ischemia-reperfusion injury via regulation of the TLR4/NF-κB signaling pathway. Pharmazie,  2014, 69(11), 850-855.
 [PMID:  25985583]

[150]
Liu, X.; Wang, Y.; Zhang, M.; Liu, Y.; Hu, L.; Gu, Y. Ticagrelor reduces ischemia-reperfusion injury through the NF-κB-dependent path-way in rats. J. Cardiovasc. Pharmacol.,  2019, 74(1), 13-19.
 [http://dx.doi.org/10.1097/FJC.0000000000000675] [PMID:  31274838]

[151]
Birnbaum, Y.; Ye, Y.; Perez-Polo, J.R. Does inhibition of nuclear factor kappa B explain the protective effect of ticagrelor on myocardial ischemia-reperfusion injury? J. Cardiovasc. Pharmacol.,  2020, 75(2), 108-111.

[152]
Xiong, W.; Zhou, R.; Qu, Y.; Yang, Y.; Wang, Z.; Song, N.; Liang, R.; Qian, J. Dexmedetomidine preconditioning mitigates myocardial ischemia/reperfusion injury via inhibition of mast cell degranulation. Biomed. Pharmacother.,  2021, 141, 111853.
 [http://dx.doi.org/10.1016/j.biopha.2021.111853] [PMID:  34237593]

[153]
Yang, Y.F.; Peng, K.; Liu, H.; Meng, X.W.; Zhang, J.J.; Ji, F.H. Dexmedetomidine preconditioning for myocardial protection in ischaemia-reperfusion injury in rats by downregulation of the high mobility group box 1-toll-like receptor 4-nuclear factor κB signalling pathway. Clin. Exp. Pharmacol. Physiol.,  2017, 44(3), 353-361.
 [http://dx.doi.org/10.1111/1440-1681.12711] [PMID:  27998004]

[154]
Zhang, J.J.; Peng, K.; Zhang, J.; Meng, X.W.; Ji, F.H. Dexmedetomidine preconditioning may attenuate myocardial ischemia/reperfusion injury by down-regulating the HMGB1-TLR4-MyD88-NF-кB signaling pathway. PLoS One,  2017, 12(2), 0172006.
 [http://dx.doi.org/10.1371/journal.pone.0172006]

[155]
Yang, J.; Jiang, H.; Yang, J.; Ding, J.W.; Chen, L.H.; Li, S.; Zhang, X.D. Valsartan preconditioning protects against myocardial ischemia-reperfusion injury through TLR4/NF-kappaB signaling pathway. Mol. Cell. Biochem.,  2009, 330(1-2), 39-46.
 [http://dx.doi.org/10.1007/s11010-009-0098-1] [PMID:  19370315]

[156]
Wu, B.; Lin, R.; Dai, R.; Chen, C.; Wu, H.; Hong, M. Valsartan attenuates oxidative stress and NF-κB activation and reduces myocardial apoptosis after ischemia and reperfusion. Eur. J. Pharmacol.,  2013, 705(1-3), 140-147.
 [http://dx.doi.org/10.1016/j.ejphar.2013.02.036] [PMID:  23499691]

[157]
Xiong, W.; Yao, M.; Zhou, R. Oxytocin ameliorates ischemia/reperfusion-induced injury by inhibiting mast cell degranulation and in-flammation in the rat heart. Biomed. Pharmacother.,  2020, 128, 110358.

[158]
Qian, X.; Zhu, M.; Qian, W.; Song, J. Vitamin D attenuates myocardial ischemia-reperfusion injury by inhibiting inflammation via sup-pressing the RhoA/ROCK/NF-ĸB pathway. Biotechnol. Appl. Biochem.,  2019, 66(5), 850-857.
 [http://dx.doi.org/10.1002/bab.1797] [PMID:  31245891]

[159]
Chen, M.; Chen, Z.; Huang, D.; Sun, C.; Xie, J.; Chen, T.; Zhao, X.; Huang, Y.; Li, D.; Wu, B.; Wu, D. Myricetin inhibits TNF-α-induced inflammation in A549 cells via the SIRT1/NF-κB pathway. Pulm. Pharmacol. Ther.,  2020, 65, 102000.
 [http://dx.doi.org/10.1016/j.pupt.2021.102000] [PMID:  33601000]

[160]
Sevilla, L.; Zaldumbide, A.; Pognonec, P.; Boulukos, K.E. Transcriptional regulation of the bcl-x gene encoding the anti-apoptotic Bcl-xL protein by Ets, Rel/NFkappaB, STAT and AP1 transcription factor families. Histol. Histopathol.,  2001, 16(2), 595-601.
 [http://dx.doi.org/10.14670/HH-16.595] [PMID:  11332715]

[161]
Li, J.; Gong, L.Y.; Song, L.B.; Jiang, L.L.; Liu, L.P.; Wu, J.; Yuan, J.; Cai, J.C.; He, M.; Wang, L.; Zeng, M.; Cheng, S.Y.; Li, M. Oncopro-tein Bmi-1 renders apoptotic resistance to glioma cells through activation of the IKK-nuclear factor-kappaB Pathway. Am. J. Pathol.,  2010, 176(2), 699-709.
 [http://dx.doi.org/10.2353/ajpath.2010.090502] [PMID:  20035051]

[162]
Hamid, T.; Gu, Y.; Ortines, R.V.; Bhattacharya, C.; Wang, G.; Xuan, Y.T.; Prabhu, S.D. Divergent tumor necrosis factor receptor-related remodeling responses in heart failure: Role of nuclear factor-kappaB and inflammatory activation. Circulation,  2009, 119(10), 1386-1397.
 [http://dx.doi.org/10.1161/CIRCULATIONAHA.108.802918] [PMID:  19255345]

[163]
Dhingra, R.; Shaw, J.A.; Aviv, Y.; Kirshenbaum, L.A. Dichotomous actions of NF-kappaB signaling pathways in heart. J. Cardiovasc. Transl. Res.,  2010, 3(4), 344-354.
 [http://dx.doi.org/10.1007/s12265-010-9195-5] [PMID:  20559771]

[164]
Lei, Q. Yi, T.; Chen, C. NF-κB-gasdermin D (GSDMD) axis couples oxidative stress and NACHT, LRR and PYD domains-containing protein 3 (NLRP3) inflammasome-mediated cardiomyocyte pyroptosis following myocardial infarction. Med. Sci. Monit.,  2018, 24(24), 6044-6052.
 [http://dx.doi.org/10.12659/MSM.908529] [PMID:  30161099]

[165]
Aoki, M.; Nata, T.; Morishita, R.; Matsushita, H.; Nakagami, H.; Yamamoto, K.; Yamazaki, K.; Nakabayashi, M.; Ogihara, T.; Kaneda, Y. Endothelial apoptosis induced by oxidative stress through activation of NF-kappaB: Antiapoptotic effect of antioxidant agents on endothe-lial cells. Hypertension,  2001, 38(1), 48-55.
 [http://dx.doi.org/10.1161/01.HYP.38.1.48] [PMID:  11463759]

[166]
Ong, S.B.; Hernández-Reséndiz, S.; Crespo-Avilan, G.E.; Mukhametshina, R.T.; Kwek, X.Y.; Cabrera-Fuentes, H.A.; Hausenloy, D.J. Inflammation following acute myocardial infarction: Multiple players, dynamic roles, and novel therapeutic opportunities. Pharmacol. Ther.,  2018, 186, 73-87.
 [http://dx.doi.org/10.1016/j.pharmthera.2018.01.001] [PMID:  29330085]

[167]
Cui, Y.; Wang, Y.; Liu, G. Protective effect of Barbaloin in a rat model of myocardial ischemia reperfusion injury through the regulation of the CNPY2 PERK pathway. Int. J. Mol. Med.,  2019, 43(5), 2015-2023.
 [http://dx.doi.org/10.3892/ijmm.2019.4123] [PMID:  30864682]

[168]
Deng, J. Advanced research on the regulated necrosis mechanism in myocardial ischemia-reperfusion injury. Int. J. Cardiol.,  2021, 334(334), 97-101.
 [http://dx.doi.org/10.1016/j.ijcard.2021.04.042] [PMID:  33930510]
Cite As
Current Protein & Peptide Science

The Role of NF-κB in Myocardial Ischemia/Reperfusion Injury

Abstract

Graphical Abstract
