The Impact of microRNAs in Renin–Angiotensin-System-Induced Cardiac Remodelling

Abstract

Current knowledge on the renin–angiotensin system (RAS) indicates its central role in the pathogenesis of cardiovascular remodelling via both hemodynamic alterations and direct growth and the proliferation effects of angiotensin II or aldosterone resulting in the hypertrophy of cardiomyocytes, the proliferation of fibroblasts, and inflammatory immune cell activation. The noncoding regulatory microRNAs has recently emerged as a completely novel approach to the study of the RAS. A growing number of microRNAs serve as mediators and/or regulators of RAS-induced cardiac remodelling by directly targeting RAS enzymes, receptors, signalling molecules, or inhibitors of signalling pathways. Specifically, microRNAs that directly modulate pro-hypertrophic, pro-fibrotic and pro-inflammatory signalling initiated by angiotensin II receptor type 1 (AT1R) stimulation are of particular relevance in mediating the cardiovascular effects of the RAS. The aim of this review is to summarize the current knowledge in the field that is still in the early stage of preclinical investigation with occasionally conflicting reports. Understanding the big picture of microRNAs not only aids in the improved understanding of cardiac response to injury but also leads to better therapeutic strategies utilizing microRNAs as biomarkers, therapeutic agents and pharmacological targets

An Insight on Multicentric Signaling of Angiotensin II in Cardiovascular system: A Recent Update

“…In brief, angiotensinogen produced from the liver is converted into Ang I and Ang II via renin, esterase-2, cathepsin G, kallikrein, chymase, and angiotensin-converting enzyme. Ubiquitous actions of Ang II can be attributed to activation of several signal transduction pathways modulated by receptors including AT 1 R and AT 2 R to initiate RAS or further get cleaved into peptides namely, Ang IV, Ang (1–7), and alamandine, which express their effects via AT4 R, Mas R and MrgD, respectively ( Adamcova et al, 2021 ; Matsubara, 1998 ). Interestingly, administration of Ang (1–7) was evidenced to provide a protective effect during chronic infusion of Ang II in rats ( Grobe et al, 2007 ).…”

“…miRNA including miR-154, miR-155, miR-132, miR-21, miR-503, miR-214, miR-19a, and miR-410 are involved in promoting hypertrophy, fibrosis, apoptosis, and inflammation. On other hand, miR-16, miR-98, miR-30a, miR-133, miR-433 possess cardio-protective effects ( Wang Q. et al, 2019 ; Song et al, 2019 ; Adamcova et al, 2021 ). Luciferase assay evidenced that miR-214 acts as a target for Long non-coding RNA (lncRNA) Plscr4 and ameliorated levels of miR-214 oppose the anti-hypertrophic effect of Plscr4 in Ang II treated cardiomyocytes via lncRNA Plscr4-miR-214-mitofusin (Mfn2) axis ( Lv et al, 2018 ).…”

N6-methyladenosine modulates long non-coding RNA in the developing mouse heart

“…It was reported that the loss of heart regenerative capacity was triggered by increasing thyroid hormones [ 13 ]. In addition, the analysis indicated that some m 6 A differential lncRNAs were also enriched in ‘insulin-like growth factor receptor’ and ‘response to angiotensin’, which are participating in cardiac hypertrophy [ 36 , 44 ]. m 6 A differential lncRNAs enriched in myocardial regeneration-related pathways, such as ‘TGF-beta signaling pathway’ is well documented [ 62 ].…”

“…Notably, postpartum relative hyperoxia inhibited glycolysis leading to halt regenerative ability [40], while hypoxia-induced anaerobic metabolism elevated glycolysis to promote regenerative milieu within the myocardium [41][42][43]. Angiotensin was known to promote interstitial cardiac fibrosis and hypertrophy [44]. In contrast, lncRNAs with down-methylated sites were involved in 'Cardiac muscle contraction' and 'Cell cycle-yeast' (Fig.…”

Chronic intracellular hypoxia as a clustering and stratifying factor for clinical severity grade in nephrotic syndrome in children

“…Data from non-renal fibroblasts suggest additional profibrotic effects of hypoxia in renal fibroblasts in suppressing apoptosis, inducing the production of proinflammatory factors and upregulating components of the renin-angiotensin system [13,14]. However, this issue has not been studied in patients with NS.…”