Endoplasmic Reticulum Stress and Renin-Angiotensin System Crosstalk in
Endothelial Dysfunction

Himanshu      Sankrityayan; Pooja   Dhileepkumar   Rao; Vishwadeep      Shelke; Yogesh   A.   Kulkarni; Shrikant   R.   Mulay; Anil   Bhanudas   Gaikwad

Abstract

Background: Vascular endothelial dysfunction (VED) significantly results in catastrophic cardiovascular diseases with multiple aetiologies. Variations in vasoactive peptides, including angiotensin II and endothelin 1, and metabolic perturbations like hyperglycaemia, altered insulin signalling, and homocysteine levels result in pathogenic signalling cascades, which ultimately lead to VED. Endoplasmic reticulum (ER) stress reduces nitric oxide availability, causes aberrant angiogenesis, and enhances oxidative stress pathways, consequently promoting endothelial dysfunction. Moreover, the renin-angiotensin system (RAS) has widely been acknowledged to impact angiogenesis, endothelial repair and inflammation. Interestingly, experimental studies at the preclinical level indicate a possible pathological link between the two pathways in the development of VED. Furthermore, pharmacological modulation of ER stress ameliorates angiotensin-II mediated VED as well as RAS intervention either through inhibition of the pressor arm or enhancement of the depressor arm of RAS, mitigating ER stress-induced endothelial dysfunction and thus emphasizing a vital crosstalk.

Conclusion: Deciphering the pathway overlap between RAS and ER stress may open potential therapeutic avenues to combat endothelial dysfunction and associated diseases. Several studies suggest that alteration in a component of RAS may induce ER stress or induction of ER stress may modulate the RAS components. In this review, we intend to elaborate on the crosstalk of ER stress and RAS in the pathophysiology of VED.

Keywords: Vascular endothelial dysfunction, endoplasmic reticulum stress, renin-angiotensin system, crosstalk, endothe-lium, angiogenesis.

Graphical Abstract

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Cite As

Current Molecular Pharmacology

Endoplasmic Reticulum Stress and Renin-Angiotensin System Crosstalk in Endothelial Dysfunction

Abstract

Graphical Abstract