Combinatorial Chemistry & High Throughput Screening

Author(s): Hongdan Wang, Bingyu Zhang, Xianhua Zhong, Dui Qin* and Zhangyong Li*

DOI: 10.2174/1386207325666220328091748

Mechanism Research of Platelet Core Marker Prediction and Molecular Recognition in Cardiovascular Events

Page: [103 - 115] Pages: 13

  • * (Excluding Mailing and Handling)

Abstract

Background: Thrombosis triggered by platelet activation plays a vital role in the pathogenesis of cardiovascular and cerebrovascular diseases.

Objective: This study aims to find platelet combined biomarkers for cardiovascular diseases and investigate the possibility of Concanavalin A (ConA) acting on platelets as a new pharmacological target.

Methods: High-throughput Technology and bioinformatics analysis were combined and groups of microarray chip gene expression profiles for acute myocardial infarction (AMI) and sickle cell disease (SCD) were obtained using GEO database screening. R language limma package was used to obtain differentially expressed genes (DEGs). GO, KEGG, and other databases were utilized to perform the enrichment analysis of DEGs’ functions, pathways, etc. PPI network was constructed using STRING database and Cytoscape software, and MCC algorithm was used to obtain the 200 core genes of the two groups of DEGs. Core targets were confirmed by constructing an intersection area screening. A type of molecular probe, ConA, was molecularly docked with the above core targets on the Zdock, HEX, and 3D-DOCK servers.

Results: We found six core markers, CD34, SOCS2, ABL1, MTOR, VEGFA, and SMURF1, which were simultaneously related to both diseases, and the docking effect showed that VEGFA is the best-performing.

Conclusion: VEGFA is most likely to reduce its expression by binding to ConA, which could affect the downstream regulation of the PI3K/Akt signaling pathway during platelet activation. Some other core targets also have the opportunity to interact with ConA to affect platelet-activated thrombosis and trigger changes in cardiovascular events.

Keywords: Cardiovascular diseases, platelet activation, gene regulation, enrichment analysis, molecular docking, sickle cell disease.

Graphical Abstract

[1]
Townsend, N.; Kazakiewicz, D.; Lucy Wright, F. Epidemiolo-gy of cardiovascular disease in Europe. Nat. Rev. Cardiol., 2021, 1-11.
[http://dx.doi.org/10.1038/s41569-021-00607-3] [PMID: 34497402]
[2]
Lordan, R.; Tsoupras, A.; Zabetakis, I. Platelet activation and prothrombotic mediators at the nexus of inflammation and atherosclerosis: Potential role of antiplatelet agents. Blood Rev., 2021, 45, 100694.
[http://dx.doi.org/10.1016/j.blre.2020.100694] [PMID: 32340775]
[3]
Aslan, J.E. platelet proteomes, pathways, and phenotypes as informants of vascular wellness and disease. Arterioscler. Thromb. Vasc. Biol., 2021, 41(3), 999-1011.
[http://dx.doi.org/10.1161/ATVBAHA.120.314647] [PMID: 33441027]
[4]
Wiwanitkit, V. Plateletcrit, mean platelet volume, platelet dis-tribution width: Its expected values and correlation with par-allel red blood cell parameters. Clin. Appl. Thromb. Hemost., 2004, 10(2), 175-178.
[http://dx.doi.org/10.1177/107602960401000208] [PMID: 15094938]
[5]
Nieswandt, B.; Pleines, I.; Bender, M. Platelet adhesion and activation mechanisms in arterial thrombosis and ischaemic stroke. J. Thromb. Haemost., 2011, 9(Suppl. 1), 92-104.
[http://dx.doi.org/10.1111/j.1538-7836.2011.04361.x] [PMID: 21781245]
[6]
Berg, D.D.; Yeh, R.W.; Mauri, L.; Morrow, D.A.; Kereiakes, D.J.; Cutlip, D.E.; Gao, Q.; Jarolim, P.; Michelson, A.D.; Frelinger, A.L., III; Cange, A.L.; Sabatine, M.S.; O’Donoghue, M.L. Biomarkers of platelet activation and cardiovascular risk in the DAPT trial. J. Thromb. Thrombolysis, 2021, 51(3), 675-681.
[http://dx.doi.org/10.1007/s11239-020-02221-5] [PMID: 32683645]
[7]
Santos-Gallego, C.G.; Badimon, J. Overview of aspirin and platelet biology. Am. J. Cardiol., 2021, 144(Suppl. 1), S2-S9.
[http://dx.doi.org/10.1016/j.amjcard.2020.12.018] [PMID: 33706986]
[8]
Wu, X.M.; Zhang, N.; Li, J.S.; Yang, Z.H.; Huang, X.L.; Yang, X.F. Purinergic receptors mediate endothelial dysfunction and participate in atherosclerosis. Purinergic Signal., 2022, 1-8.
[http://dx.doi.org/10.1007/s11302-021-09839-x] [PMID: 34981330]
[9]
Alenazy, F.O.; Thomas, M.R. Novel antiplatelet targets in the treatment of acute coronary syndromes. Platelets, 2021, 32(1), 15-28.
[http://dx.doi.org/10.1080/09537104.2020.1763731] [PMID: 32529932]
[10]
Nording, H.; Baron, L.; Langer, H.F. Platelets as therapeutic targets to prevent atherosclerosis. Atherosclerosis, 2020, 307, 97-108.
[http://dx.doi.org/10.1016/j.atherosclerosis.2020.05.018] [PMID: 32653088]
[11]
Schulz, C.; Penz, S.; Hoffmann, C.; Langer, H.; Gillitzer, A.; Schneider, S.; Brandl, R.; Seidl, S.; Massberg, S.; Pichler, B.; Kremmer, E.; Stellos, K.; Schönberger, T.; Siess, W.; Gawaz, M. Platelet GPVI binds to collagenous structures in the core region of human atheromatous plaque and is critical for atheroprogression in vivo. Basic Res. Cardiol., 2008, 103(4), 356-367.
[http://dx.doi.org/10.1007/s00395-008-0722-3] [PMID: 18431526]
[12]
Senis, Y.A.; Mazharian, A.; Mori, J. Src family kinases: At the forefront of platelet activation. Blood, 2014, 124(13), 2013-2024.
[http://dx.doi.org/10.1182/blood-2014-01-453134] [PMID: 25115887]
[13]
Busygina, K.; Jamasbi, J.; Seiler, T.; Deckmyn, H.; Weber, C.; Brandl, R.; Lorenz, R.; Siess, W. Oral Bruton tyrosine kinase inhibitors selectively block atherosclerotic plaque-triggered thrombus formation in humans. Blood, 2018, 131(24), 2605-2616.
[http://dx.doi.org/10.1182/blood-2017-09-808808] [PMID: 29559479]
[14]
Goldmann, L.; Duan, R.; Kragh, T.; Wittmann, G.; Weber, C.; Lorenz, R.; von Hundelshausen, P.; Spannagl, M.; Siess, W. Oral Bruton tyrosine kinase inhibitors block activation of the platelet Fc receptor CD32a (FcγRIIA): A new option in HIT? Blood Adv., 2019, 3(23), 4021-4033.
[http://dx.doi.org/10.1182/bloodadvances.2019000617] [PMID: 31809536]
[15]
Montalban, X.; Arnold, D.L.; Weber, M.S.; Staikov, I.; Pias-ecka-Stryczynska, K.; Willmer, J.; Martin, E.C.; Dangond, F.; Syed, S.; Wolinsky, J.S. Placebo-controlled trial of an oral BTK inhibitor in multiple sclerosis. N. Engl. J. Med., 2019, 380(25), 2406-2417.
[http://dx.doi.org/10.1056/NEJMoa1901981] [PMID: 31075187]
[16]
Treon, S.P.; Castillo, J.J.; Skarbnik, A.P.; Soumerai, J.D.; Ghobrial, I.M.; Guerrera, M.L.; Meid, K.; Yang, G. The BTK inhibitor ibrutinib may protect against pulmonary injury in COVID-19-infected patients. Blood, 2020, 135(21), 1912-1915.
[http://dx.doi.org/10.1182/blood.2020006288] [PMID: 32302379]
[17]
Borst, O.; Münzer, P.; Gatidis, S.; Schmidt, E.M.; Schön-berger, T.; Schmid, E.; Towhid, S.T.; Stellos, K.; Seizer, P.; May, A.E.; Lang, F.; Gawaz, M. The inflammatory chemokine CXC motif ligand 16 triggers platelet activation and adhesion via CXC motif receptor 6-dependent phosphatidylinositide 3-kinase/Akt signaling. Circ. Res., 2012, 111(10), 1297-1307.
[http://dx.doi.org/10.1161/CIRCRESAHA.112.276444] [PMID: 22927331]
[18]
Chatterjee, M.; Borst, O.; Walker, B.; Fotinos, A.; Vogel, S.; Seizer, P.; Mack, A.; Alampour-Rajabi, S.; Rath, D.; Geisler, T.; Lang, F.; Langer, H.F.; Bernhagen, J.; Gawaz, M. Macro-phage migration inhibitory factor limits activation-induced apoptosis of platelets via CXCR7-dependent Akt signaling. Circ. Res., 2014, 115(11), 939-949.
[http://dx.doi.org/10.1161/CIRCRESAHA.115.305171] [PMID: 25266363]
[19]
Blair, T.A.; Moore, S.F.; Hers, I. Circulating primers enhance platelet function and induce resistance to antiplatelet therapy. J. Thromb. Haemost., 2015, 13(8), 1479-1493.
[http://dx.doi.org/10.1111/jth.13022] [PMID: 26039631]
[20]
Blair, T.A.; Moore, S.F.; Walsh, T.G.; Hutchinson, J.L.; Dur-rant, T.N.; Anderson, K.E.; Poole, A.W.; Hers, I. Phospho-inositide 3-kinase p110α negatively regulates thrombopoietin-mediated platelet activation and thrombus formation. Cell. Signal., 2018, 50, 111-120.
[http://dx.doi.org/10.1016/j.cellsig.2018.05.005] [PMID: 29793021]
[21]
Davizon-Castillo, P.; McMahon, B.; Aguila, S.; Bark, D.; Ashworth, K.; Allawzi, A.; Campbell, R.A.; Montenont, E.; Nemkov, T.; D’Alessandro, A.; Clendenen, N.; Shih, L.; Sanders, N.A.; Higa, K.; Cox, A.; Padilla-Romo, Z.; Hernan-dez, G.; Wartchow, E.; Trahan, G.D.; Nozik-Grayck, E.; Jones, K.; Pietras, E.M.; DeGregori, J.; Rondina, M.T.; Di Paola, J. TNF-α-driven inflammation and mitochondrial dys-function define the platelet hyperreactivity of aging. Blood, 2019, 134(9), 727-740.
[http://dx.doi.org/10.1182/blood.2019000200] [PMID: 31311815]
[22]
Biswas, S.; Xin, L.; Panigrahi, S.; Zimman, A.; Wang, H.; Yakubenko, V.P.; Byzova, T.V.; Salomon, R.G.; Podrez, E.A. Novel phosphatidylethanolamine derivatives accumulate in circulation in hyperlipidemic ApoE-/- mice and activate plate-lets via TLR2. Blood, 2016, 127(21), 2618-2629.
[http://dx.doi.org/10.1182/blood-2015-08-664300] [PMID: 27015965]
[23]
Nording, H.; Langer, H.F. Complement links platelets to innate immunity. In: Seminars in immunology; 43-52.
[http://dx.doi.org/10.1016/j.smim.2018.01.003]
[24]
Suzuki-Inoue, K.; Tsukiji, N.; Shirai, T. Platelet CLEC-2: Roles beyond hemostasis. Semin. Thromb. Hemost., 2018, 44(02), 126-134.
[http://dx.doi.org/10.1055/s-0037-1604090]
[25]
Kurihara, Y.; Hosoya, H.; Kishihara, R.; Yoshinaga, M.; Iwa-date, Y.; Yamauchi, F.; Saito, T.; Sakurai, K. Comparison of the effects of pre-dilution and post-dilution online hemodia-filtration on the levels of inflammatory markers, lympho-cytes, and platelets. J. Artif. Organs, 2021, 1-7.
[http://dx.doi.org/10.1007/s10047-021-01281-5] [PMID: 34128110]
[26]
Wohner, N.; Sebastian, S.; Muczynski, V.; Huskens, D.; de Laat, B.; de Groot, P.G.; Lenting, P.J. Osteoprotegerin modulates platelet adhesion to von Willebrand factor during release from endothelial cells. J. Thromb. Haemost., 2021, jth.15598.
[http://dx.doi.org/10.1111/jth.15598] [PMID: 34816579]
[27]
Berger Fridman, I.; Ugolini, G.S.; VanDelinder, V.; Cohen, S.; Konry, T. High throughput microfluidic system with multiple oxygen levels for the study of hypoxia in tumor spheroids. Biofabrication, 2021, 13(3), 035037.
[http://dx.doi.org/10.1088/1758-5090/abdb88] [PMID: 33440359]
[28]
Su, J.; Gao, C.; Wang, R.; Xiao, C.; Yang, M. Genes associat-ed with inflammation and the cell cycle may serve as bi-omarkers for the diagnosis and prognosis of acute myocardial infarction in a Chinese population. Mol. Med. Rep., 2018, 18(2), 1311-1322.
[http://dx.doi.org/10.3892/mmr.2018.9077] [PMID: 29845217]
[29]
Chen, H.; Chen, Y.; Wang, X.; Yang, J.; Huang, C. Edaravone attenuates myocyte apoptosis through the JAK2/STAT3 pathway in acute myocardial infarction. Free Radic. Res., 2020, 54(5), 351-359.
[http://dx.doi.org/10.1080/10715762.2020.1772469] [PMID: 32543312]
[30]
Wang, C.; Li, Q.; Yang, H.; Gao, C.; Du, Q.; Zhang, C.; Zhu, L.; Li, Q. MMP9, CXCR1, TLR6, and MPO participant in the progression of coronary artery disease. J. Cell. Physiol., 2020, 235(11), 8283-8292.
[http://dx.doi.org/10.1002/jcp.29485] [PMID: 32052443]
[31]
Santoro, S.A. Differential effects of concanavalin A and suc-cinyl concanavalin A on the macromolecular events of plate-let activation. Biochim. Biophys. Acta, 1983, 757(1), 101-110.
[http://dx.doi.org/10.1016/0304-4165(83)90157-5] [PMID: 6682338]
[32]
Painter, R.G.; Ginsberg, M. Concanavalin A induces interac-tions between surface glycoproteins and the platelet cytoskel-eton. J. Cell Biol., 1982, 92(2), 565-573.
[http://dx.doi.org/10.1083/jcb.92.2.565] [PMID: 6460776]
[33]
Pan, M.; Zhang, J. Quantile normalization for combining gene-expression datasets. Biotechnol. Biotechnol. Equip., 2018, 32(3), 751-758.
[http://dx.doi.org/10.1080/13102818.2017.1419376]
[34]
Jin, S.H.; Zhou, R.H.; Guan, X.Y.; Zhou, J.G.; Liu, J.G. Iden-tification of novel key lncRNAs involved in periodontitis by weighted gene co-expression network analysis. J. Periodontal Res., 2020, 55(1), 96-106.
[http://dx.doi.org/10.1111/jre.12693] [PMID: 31512745]
[35]
Lewis, B.P.; Burge, C.B.; Bartel, D.P. Conserved seed pairing, often flanked by adenosines, indicates that thousands of hu-man genes are microRNA targets. Cell, 2005, 120(1), 15-20.
[http://dx.doi.org/10.1016/j.cell.2004.12.035] [PMID: 15652477]
[36]
Betel, D.; Koppal, A.; Agius, P.; Sander, C.; Leslie, C. Com-prehensive modeling of microRNA targets predicts functional non-conserved and non-canonical sites. Genome Biol., 2010, 11(8), R90.
[http://dx.doi.org/10.1186/gb-2010-11-8-r90] [PMID: 20799968]
[37]
Chen, Y.; Wang, X. miRDB: An online database for prediction of functional microRNA targets. Nucleic Acids Res., 2020, 48(D1), D127-D131.
[http://dx.doi.org/10.1093/nar/gkz757] [PMID: 31504780]
[38]
Athanasios, A.; Charalampos, V.; Vasileios, T.; Ashraf, G.M. Protein-protein interaction (PPI) network: Recent advances in drug discovery. Curr. Drug Metab., 2017, 18(1), 5-10.
[http://dx.doi.org/10.2174/138920021801170119204832] [PMID: 28889796]
[39]
Yang, Q.; Li, K.; Li, X.; Liu, J. Identification of key genes and pathways in myeloma side population cells by bioinformatics analysis. Int. J. Med. Sci., 2020, 17(14), 2063-2076.
[http://dx.doi.org/10.7150/ijms.48244] [PMID: 32922167]
[40]
Benjamin; Webb, ; Andrej, ; Sali, Protein structure modeling with modeller. In: Methods in Molecular Biology, 2017, 426, pp. 145-159.
[41]
Najibi, S.M.; Maadooliat, M.; Zhou, L. 2017 Protein structure classification and loop modeling using multiple Ramachan-dran distributions. Comput. Struct. Biotechnol. J., 15, 243-254.
[http://dx.doi.org/10.1016/j.csbj.2017.01.011]
[42]
Esfandi, B.; Atabati, M. Sequential Dihedral Angles (SDAs): A Method for Evaluating the 3D Structure of Proteins. Protein J., 2021, 40(1), 1-7.
[http://dx.doi.org/10.1007/s10930-020-09961-6] [PMID: 33442828]
[43]
Paolisso, P.; Foà, A.; Bergamaschi, L.; Donati, F.; Fabrizio, M.; Chiti, C.; Angeli, F.; Toniolo, S.; Stefanizzi, A.; Armillot-ta, M.; Rucci, P.; Iannopollo, G.; Casella, G.; Marrozzini, C.; Galiè, N.; Pizzi, C. Hyperglycemia, inflammatory response and infarct size in obstructive acute myocardial infarction and MINOCA. Cardiovasc. Diabetol., 2021, 20(1), 33.
[http://dx.doi.org/10.1186/s12933-021-01222-9] [PMID: 33530978]
[44]
Lin, H.J.; Wang, T.D. Profiling the evolution of inflammatory response and exploring its prognostic significance in acute myocardial infarction: The first step to establishing anti-inflammatory strategy. Zhonghua Minguo Xinzangxue Hui Zazhi, 2017, 33(5), 486-488.
[http://dx.doi.org/10.6515/ACS20170731A] [PMID: 28959100]
[45]
Cognasse, F.; Laradi, S.; Berthelot, P.; Bourlet, T.; Marotte, H.; Mismetti, P.; Garraud, O.; Hamzeh-Cognasse, H. Platelet inflammatory response to stress. Front. Immunol., 2019, 10, 1478.
[http://dx.doi.org/10.3389/fimmu.2019.01478] [PMID: 31316518]
[46]
Hally, K.E.; La Flamme, A.C.; Larsen, P.D.; Harding, S.A. Platelet Toll-like receptor (TLR) expression and TLR-mediated platelet activation in acute myocardial infarction. Thromb. Res., 2017, 158, 8-15.
[http://dx.doi.org/10.1016/j.thromres.2017.07.031] [PMID: 28783513]
[47]
Kwon, H.W. Inhibitory effects of ginsenoside Ro on clot retraction through suppressing PI3K/Akt signaling pathway in human platelets. Prev. Nutr. Food Sci., 2019, 24(1), 56-63.
[http://dx.doi.org/10.3746/pnf.2019.24.1.56] [PMID: 31008097]
[48]
Irfan, M.; Jeong, D.; Kwon, H.W. Ginsenoside-Rp3 inhibits platelet activation and thrombus formation by regulating MAPK and cyclic nucleotide signaling. Vascul. Pharmacol., 2018, 109, 45-55.
[http://dx.doi.org/10.1016/j.vph.2018.06.002]
[49]
Guidetti, G.F.; Canobbio, I.; Torti, M. PI3K/Akt in platelet integrin signaling and implications in thrombosis. Adv. Biol. Regul., 2015, 59, 36-52.
[http://dx.doi.org/10.1016/j.jbior.2015.06.001] [PMID: 26159296]
[50]
Chen, X.; Zhang, Y.; Wang, Y.; Li, D.; Zhang, L.; Wang, K.; Luo, X.; Yang, Z.; Wu, Y.; Liu, J. PDK1 regulates platelet ac-tivation and arterial thrombosis. Blood, 2013, 121(18), 3718-3726.
[http://dx.doi.org/10.1182/blood-2012-10-461897] [PMID: 23444402]
[51]
Leonard, A.; Bonifacino, A.; Dominical, V.M.; Luo, M.; Haro-Mora, J.J.; Demirci, S.; Uchida, N.; Pierciey, F.J., Jr; Tisdale, J.F. Bone marrow characterization in sickle cell dis-ease: Inflammation and stress erythropoiesis lead to subop-timal CD34 recovery. Br. J. Haematol., 2019, 186(2), 286-299.
[http://dx.doi.org/10.1111/bjh.15902] [PMID: 30972754]
[52]
Dull, K.; Fazekas, F. Törőcsik, D. Factor XIII-A in diseases: Role beyond blood coagulation. Int. J. Mol. Sci., 2021, 22(3), 1459.
[http://dx.doi.org/10.3390/ijms22031459] [PMID: 33535700]
[53]
Marneth, A.E.; van Heerde, W.L.; Hebeda, K.M.; Laros-van Gorkom, B.A.; Barteling, W.; Willemsen, B.; de Graaf, A.O.; Simons, A.; Jansen, J.H.; Preijers, F.; Jongmans, M.C.; van der Reijden, B.A. Platelet CD34 expression and α/δ-granule abnormalities in GFI1B- and RUNX1-related familial bleeding disorders. Blood, 2017, 129(12), 1733-1736.
[http://dx.doi.org/10.1182/blood-2016-11-749366] [PMID: 28096094]
[54]
Suurmeijer, A.J.H.; Dickson, B.C.; Swanson, D.; Zhang, L.; Sung, Y.S.; Cotzia, P.; Fletcher, C.D.M.; Antonescu, C.R. A novel group of spindle cell tumors defined by S100 and CD34 co-expression shows recurrent fusions involving RAF1, BRAF, and NTRK1/2 genes. Genes Chromosomes Cancer, 2018, 57(12), 611-621.
[http://dx.doi.org/10.1002/gcc.22671] [PMID: 30276917]
[55]
Vila Ellis, L.; Cain, M.P.; Hutchison, V.; Flodby, P.; Crandall, E.D.; Borok, Z.; Zhou, B.; Ostrin, E.J.; Wythe, J.D.; Chen, J. Epithelial vegfa specifies a distinct endothelial population in the mouse lung. Dev. Cell, 2020, 52(5), 617-630.e6.
[http://dx.doi.org/10.1016/j.devcel.2020.01.009] [PMID: 32059772]
[56]
Chen, H.X.; Xu, X.X.; Tan, B.Z.; Zhang, Z.; Zhou, X.D. Mi-croRNA-29b inhibits angiogenesis by targeting VEGFA through the MAPK/ERK and PI3K/Akt signaling pathways in endometrial carcinoma. Cell. Physiol. Biochem., 2017, 41(3), 933-946.
[http://dx.doi.org/10.1159/000460510] [PMID: 28222438]
[57]
Wu, H.; Wei, M.; Jiang, X.; Tan, J.; Xu, W.; Fan, X.; Zhang, R.; Ding, C.; Zhao, F.; Shao, X.; Zhang, Z.; Shi, R.; Zhang, W.; Wu, G. lncRNA PVT1 promotes tumorigenesis of colo-rectal cancer by stabilizing miR-16-5p and interacting with the VEGFA/VEGFR1/AKT axis. Mol. Ther. Nucleic Acids, 2020, 20, 438-450.
[http://dx.doi.org/10.1016/j.omtn.2020.03.006] [PMID: 32276209]
[58]
Liang, C.; Zhang, L.; Lian, X.; Zhu, T.; Zhang, Y.; Gu, N. Circulating exosomal SOCS2-AS1 acts as a novel biomarker in predicting the diagnosis of coronary artery disease. BioMed Res. Int., 2020, 2020, 9182091.
[http://dx.doi.org/10.1155/2020/9182091] [PMID: 32352013]
[59]
Zhang, W.; Xiong, Z.; Wei, T.; Li, Q.; Tan, Y.; Ling, L.; Feng, X. Nuclear factor 90 promotes angiogenesis by regulating HIF-1α/VEGF-A expression through the PI3K/Akt signaling pathway in human cervical cancer. Cell Death Dis., 2018, 9(3), 276.
[http://dx.doi.org/10.1038/s41419-018-0334-2] [PMID: 29449553]
[60]
Tao, S.C.; Guo, S.C.; Zhang, C.Q. Platelet-derived extracellu-lar vesicles: An emerging therapeutic approach. Int. J. Biol. Sci., 2017, 13(7), 828-834.
[http://dx.doi.org/10.7150/ijbs.19776] [PMID: 28808416]
[61]
Wang, Y.; Xie, Y.; Zhang, A. 2019 Exosomes: An emerging factor in atherosclerosis. Biomed. Pharmacother., 115, 10895.
[http://dx.doi.org/10.1016/j.biopha.2019.108951]
[62]
Sharda, S.; Sarmandal, P.; Cherukommu, S.; Dindhoria, K.; Yadav, M.; Bandaru, S.; Sharma, A.; Sakhi, A.; Vyas, T.; Hussain, T.; Nayarisseri, A.; Singh, S.K. A virtual screening approach for the identification of high affinity small mole-cules targeting BCR-ABL1 inhibitors for the treatment of chronic myeloid leukemia. Curr. Top. Med. Chem., 2017, 17(26), 2989-2996.
[http://dx.doi.org/10.2174/1568026617666170821124512] [PMID: 28828991]
[63]
Pouwer, M.G.; Pieterman, E.J.; Verschuren, L.; Caspers, M.P.M.; Kluft, C.; Garcia, R.A.; Aman, J.; Jukema, J.W.; Prin-cen, H.M.G. The BCR-ABL1 inhibitors imatinib and ponatinib decrease plasma cholesterol and atherosclerosis, and nilotinib and ponatinib activate coagulation in a transla-tional mouse mode. Front. Cardiovasc. Med., 2018, 5, 55.
[http://dx.doi.org/10.3389/fcvm.2018.00055] [PMID: 29946549]
[64]
Guo, J.; Qiu, X.; Zhang, L.; Wei, R. Smurf1 regulates macro-phage proliferation, apoptosis and migration via JNK and p38 MAPK signaling pathways. Mol. Immunol., 2018, 97, 20-26.
[http://dx.doi.org/10.1016/j.molimm.2018.03.005] [PMID: 29550577]
[65]
Tajbakhsh, A.; Bianconi, V.; Pirro, M.; Gheibi Hayat, S.M.; Johnston, T.P.; Sahebkar, A. Efferocytosis and atherosclero-sis: Regulation of phagocyte function by MicroRNAs. Trends Endocrinol. Metab., 2019, 30(9), 672-683.
[http://dx.doi.org/10.1016/j.tem.2019.07.006] [PMID: 31383556]
[66]
Signorello, M.G.; Leoncini, G. The molecular mechanisms involved in lectin-induced human platelet aggregation. Biol. Chem., 2017, 398(12), 1335-1346.
[http://dx.doi.org/10.1515/hsz-2017-0115] [PMID: 28779561]