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

Abstract

Background: Vascular endothelial dysfunction (VED) significantly results in catastrophic car-diovascular diseases with multiple aetiologies. Variations in vasoactive peptides, including angiotensin II and endothelin 1, and metabolic perturbations like hyperglycaemia, altered insulin signalling, and homo-cysteine levels result in pathogenic signalling cascades, which ultimately lead to VED. Endoplasmic re-ticulum (ER) stress reduces nitric oxide availability, causes aberrant angiogenesis, and enhances oxidative stress pathways, consequently promoting endothelial dysfunction. Moreover, the renin-angiotensin sys-tem (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 dys-function and thus emphasizing a vital crosstalk. Conclusion: Deciphering the pathway overlap between RAS and ER stress may open potential therapeu-tic avenues to combat endothelial dysfunction and associated diseases. Several studies suggest that alter-ation 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 patho-physiology of VED.