Regulation of circular RNA Cdr1as in mediating myocardial fibrosis and ventricular remodeling of spontaneous hypertension rats by the TGF-β1/Smad signaling pathway

YU Qin; LIU Chaoqun; ZHONG Xiaolan

doi:10.3969/j.issn.1002-7386.2026.02.007

Abstract：Objective To explore the mechanisms of circular RNA Cdr1as(circRNA Cdr1as)in mediating myocardial fibrosis and ventricular remodeling in spontaneous hypertension rats(SHR)by regulating the transforming growth factor(TGF)-β1/Smad signaling pathway.Methods A total of 30 SHR rats and 15 Wistar rats(control group),male or female,with an average weight of(275.45±10.96)g,were selected.SHR rats were randomly divided into the model group,and circRNA Cdr1as over-expression group,with 15 rats in each group.The systolic blood pressure(SBP)was measured on day 1,and on days 21 and 42.Enzyme-linked immunosorbent assay(ELISA)was used to detect plasma creatine kinase isoenzymes(CK-MB),cardiac troponin(cTnI),type B brain natriuretic peptide(BNP),and angiotensin Ⅱ(Ang Ⅱ).Left ventricular posterior wall thickness at end-diastole and end-systole(LVPWd and LVPWs)were measured by echocardiography.The thickness of apical myocardial tissue was measured and left ventricular mass index(LVMI)was calculated.Masson staining was used to calculate myocardial collagen volume fraction(CVF).The quantitative reverse-transcription polymerase chain reaction(qRT-PCR)was used to detect type I and Ⅲ collagen(Col I and Col-Ⅲ),and circRNA Cdr1as in myocardial tissues.Western blot was used to detect protein levels of TGF-β1 and p-Smad 3 in myocardial tissues.Results The systolic blood pressure,serum AngⅡ,LVPWd,LVPWs,thickness of myocardial tissue at the apex,LVMI,CVF,Col-ⅠmRNA,Col-ⅢmRNA,myocardial CircRNA Cdr1as mRNA,TGF-β1 and p-Smad 3 protein levels in the overexpression group,model group and control group on the 1st,21st and 42nd days all showed a gradually increasing trend,with the overexpression group showing the most significant increase(all P<0.05).There were statistically significant differences in systolic blood pressure,serum AngⅡ,LVPWd,LVPWs,thickness of myocardial tissue at the apex,LVMI,CVF,Col-ⅠmRNA,Col-ⅢmRNA,myocardial CircRNA Cdr1as mRNA,TGF-β1 and p-Smad 3 protein levels among the three groups,at different time points and in the interaction between groups and time points(all P<0.05).Conclusion Overexpression of circRNA Cdr1as can increase blood pressure,and induce myocardial fibrosis,and ventricular remodeling in SHR rats by regulating the TGF-β1/Smad signaling pathway.