Downregulated microRNA‑133a induces HUVECs injury: Potential role of the (pro) renin receptor in angiotensin�II‑dependent hypertension

Abstract

The renin-angiotensin system (RAS) serves an essential role in hypertension. MicroRNAs (miRs) have been reported to be important regulators in angiotensin (Ang) II-dependent hypertension. We aimed to explore the roles of Ang II and miR-133a in the mechanism underlying hypertension. Human umbilical vein endothelial cells (HUVECs) were identified by immunofluorescence staining. Cell viability and miR-133a expression under the inhibition of Ang II of various concentrations were determined by an MTT assay and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. The effects of HUVECs transfected with miR-133a mimic or inhibitor on Ang II-induced apoptosis were measured using flow cytometry. The potential targeting of miR-133a to the 3′ untranslated region of (pro) renin receptor (PRR) was assessed using TargetScan and a dual-luciferase assay. The effects of PRR interference using small interfering (si)RNA on PRR expression and the rate of apoptosis were determined by RT-qPCR, western blotting and flow cytometry, respectively. Ang II at a concentration of 10 −5 M significantly inhibited the cell viability (P<0.05) and miR-133a expression (P<0.01); Downregulation of miR-133a suppressed cell viability. HUVECs transfected with miR-133a mimic reduced the rate of Ang II-induced apoptosis from 21.99 to 12.38%, but miR-133a inhibitor promoted Ang II-induced apoptosis (apoptosis rate, 28.9%). PRR was predicted to be a target gene of miR-133a. Transfection with siPRR decreased the apoptotic rate in Ang II + negative control and Ang II + miR-133a inhibitor group to 11.39 and 12.94%, respectively. Our findings also suggested that Ang II promoted PRR expression to enhance the apoptotic rate of HUVECs via the suppression of miR-133a. Furthermore, siPRR efficiently decreased the Ang II-induced apoptosis.

LncRNA SNHG12 alleviates hypertensive vascular endothelial injury through miR-25-3p/SIRT6 pathway

“…Numerous researches have provided evidence that miRNAs negatively regulate mRNA expression through binding to the 3′‐untranslated region of target mRNAs, thereby modulating vascular EC injury in Ang II‐induced HPT 35–37 . MiR‐25‐3p, a member of the miR‐17‐92 cluster, promotes vascular permeability through targeting KLF2 and KLF4 in ECs 38 .…”

Human Cell Modeling for Cardiovascular Diseases

“…Emerging technologies will allow in the future an increasingly precise understanding of the pathophysiology of CVDs and consequent therapeutic advancements. Arrhythmogenic Cardiomyopathy Pathogenic mechanism [8] BMCs Arrhythmogenic Cardiomyopathy Pathogenic mechanism [10] Heart failure - [11] CMs Heart failure Pathogenic mechanism [14] Hypertrophic Cardiomyopathy Drug discovery [16,17] C-MSCs Myocardial ischemia Pathogenic mechanism [24] Arrhythmogenic Cardiomyopathy Pathogenic mechanism/Involvement in disease pathogenesis [25] c-kit + C-MSCs Atrial Fibrillation Pathogenic mechanism [31] FAPs Arrhythmogenic Cardiomyopathy Involvement in disease pathogenesis [35] ECs Hypertension Pathogenic mechanism [39,43] Atherosclerosis Pathogenic mechanism/Involvement in disease pathogenesis [41] Pathogenic mechanism [42] VSMCs Hypertension Involvement in disease pathogenesis [48] Pathogenic mechanism [49] Atherosclerosis Differentiation phenotypes [46] Pathogenic mechanism/Drug discovery [47] AC 16 Hypertrophic Cardiomyopathy Drug discovery [51] Myocardial ischemia Pathogenic mechanism [52] hESC-CMs Hypertrophic Cardiomyopathy Pathogenic mechanism [64,65] hiPSC-CMs Atrial Fibrillation Pathogenic mechanism [76] Hypertrophic Cardiomyopathy Drug discovery [78] Long QT Syndrome Pathogenic mechanism/Drug discovery [79] hiPSC-ECs Hypertension Drug discovery [81] Moyamoya disease Pathogenic mechanism [82] hiPSC-SMCs Supravalvular aortic stenosis syndrome Pathogenic mechanism [83] Bicuspid Aortic Valve-related Thoracic Aortic Aneurysm Pathogenic mechanism/Drug discovery [84] VSMCs and CD14 + cells co-culture Atherosclerosis Pathogenic mechanism [88] [89] ECs and VSMCs co-culture Atherosclerosis Pathogenic mechanism [90]...…”

“…The group discovered that increasing concentrations of Ang II inhibited miR-133 expression and that a downregulation and an upregulation of miR-133 suppressed and enhanced HUVECs viability, respectively. They hypothesized the target of miR-133 being pro—renin receptor (PRR), whose silencing decreased Ang II-induced apoptosis [ 39 ]. Since arterial and venous ECs have different embryonic origins and show distinct molecular and functional identities, it can be opportune to choose accurately the endothelial subtype to model a CVD [ 40 ].…”

Cardiovascular aspects of the (pro)renin receptor: Function and significance

“…The binding of exogenous prorenin to vascular EC PRR contributes to pERK1/2 in a MEK‐dependent and RAS‐independent manner, resulting in the proliferation, migration, and tube formation of vascular EC 22 . Besides, AngII enhanced the apoptotic rate of human umbilical vein endothelial cells (HUVEC) by promoting PRR expression, as characterized by that PRR knockdown by siRNA efficiently blocked the AngII‑induced apoptosis of HUVEC 70 . sPRR is presented in the culture medium of HUVEC and reported to bind and activate recombinant human prorenin protein in vitro 23 .…”