Cardiovascular Disease, Single Nucleotide Polymorphisms; and the Renin Angiotensin System: Is There a MicroRNA Connection?

Abstract

Essential hypertension is a complex disorder, caused by the interplay between many genetic variants, gene-gene interactions, and environmental factors. Given that the renin-angiotensin system (RAS) plays an important role in blood pressure (BP) control, cardiovascular regulation, and cardiovascular remodeling, special attention has been devoted to the investigation of single-nucleotide polymorphisms (SNP) harbored in RAS genes that may be associated with hypertension and cardiovascular disease. MicroRNAs (miRNAs) are a family of small, ∼21-nucleotide long, and nonprotein-coding RNAs that recognize target mRNAs through partial complementary elements in the 3′-untranslated region (3′-UTR) of mRNAs and inhibit gene expression by targeting mRNAs for translational repression or destabilization. Since miRNA SNPs (miRSNPs) can create, destroy, or modify miRNA binding sites, this review focuses on the hypothesis that transcribed target SNPs harbored in RAS mRNAs, that alter miRNA gene regulation and consequently protein expression, may contribute to cardiovascular disease susceptibility.

Aldosterone Regulates MicroRNAs in the Cortical Collecting Duct to Alter Sodium Transport

“…[52][53][54][55][56][57][58][59][60] In the kidney, miRs have been linked to diabetic nephropathy, polycystic kidney disease, renal cancer, AKI, transplant rejection, and kidney development. 59,[61][62][63][64][65][66] Recently, several studies have focused on the role of miR-192, an miR known to be expressed in the kidney cortex, in the profibrotic progression of nephropathy.…”

Eccentric and concentric cardiac hypertrophy induced by exercise training: microRNAs and molecular determinants

“…Experiments involving transfection of cells that mimic mature miR-155 showed that this miR inhibited the expression of human AT1 receptor and also attenuated Ang II-induced signaling via the AT1 receptor in fibroblasts and VSMCs. Other experiments with antimir have demonstrated that transfection of anti-miR-155 increased AT1 receptor expression and also enhanced Ang II signaling via this receptor (60). Despite the fact that the literature has presented studies discussing the relationship of miRs and cardiac hypertrophy in cardiovascular disease and phenotypes, it is important to emphasize that, to our knowledge, only one study involving cardiac hypertrophy induced by physical training and miRs has been published, and the differential expression between the types of cardiac hypertrophy (physiological vs pathological) has not been explored.…”

Association of +1245 A/G MT1A and -209 A/G MT2A Polymorphysms with Coronary Artery Disease and Diabetes Mellitus in Bulgarian Cohort

“…It has been found that SNPs could affect the protein structure, changing their amino-acid sequence or interfering with their regulation (5). Three different SNPs (rs11640851, rs8052394 and rs1610216) in MT genes were shown to be associated with diabetes and its complications (8,6,22).…”