Purpose: Previous studies found that piRNAs could participate in disease progression by regulating DNA methylation, but there are few reports on their roles in heart failure (HF). Methods: The level of piRNA-6426 in the venous blood of HF patients and volunteers was detected by RT-qPCR. Hypoxia-induced cardiomyocytes were transfected with lentiviral-mediated piRNA-6426 overexpression vector (LV-piRNA-6426) or together with LV-DNMT3B, and then cell viability and apoptosis, glucose uptake, ROS production, LDH activity and secretion of inflammatory factors were detected. Also, cardiomyocytes were transfected with LV-piRNA-6426, sh-piRNA-6426 or sh-SOAT1, as well as LV-piRNA-6426 or together with LV-DNMT3B or sh-DNMT3B. The interaction between piRNA-6426 and methyltransferase 3B (DNMT3B) was detected with RNA immunoprecipitation (RIP). And the methylation level of sterol o-acyltransferase 1 (SOAT1) and the enrichment of DNMT3B in the SOAT1 promoter were detected with Methylation-specific PCR (MSP) and ChIP assays. Then a HF rat model constructed with coronary artery occlusion method was injected with LV-piRNA-6426, and heart function index and infarcted area of rat heart were detected. Results: piRNA-6426 expression was decreased in the blood of HF patients. LV-piRNA-6426 transfection increased the enrichment of DNMT3B in SOAT1 promoter, thereby inhibiting the expression level of SOAT1, and decreased hypoxia-induced oxidative stress and inflammation in cardiomyocytes, while sh-piRNA-6426 transfection had the opposite effect. And LV-DNMT3B transfection enhanced the effect of LV-piRNA-6426 transfection on SOAT1 expression and cardiomyocyte dysfunction. Injection of LV-piRNA-6426 significantly inhibited the heart dysfunction of rats. Conclusions: piRNA-6426 overexpression inhibits hypoxia-induced cardiomyocyte dysfunction and HF by promoting DNMT3B-mediated methylation of SOAT1 promoter.

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BackgroundSelenium (Se) deficiency and supplementation result in multiple effects. GPx-1 (Pro198Leu) polymorphism is associated with Se deficiency. This study aimed to observe associations between Se-deficiency/supplement and GPx-1-198Leu overexpression in myocardial injuries.Material/MethodsGPx-1P198L transgenic (Tg) mice and non-transgenic wild-type (WT) littermates were divided into Control (CON, 0.1–0.2 mg/kg), Se-deficiency (SD, <0.02 mg/kg), and Se-supplement (SS, 0.4 mg/kg) groups. Cardiac functions were observed with animal M-mode echocardiography. Se level was measured using 2,3-diamino Kenai fluorospectrophotometry. Total cardiac GPx activity was also measured. Myocardial histopathology was determined with HE and Masson’s trichrome staining. Caspase-9 and caspase-3 were measured with Western blot analysis.ResultsIn WT Se-deficient mice, cardiac GPx activity was significantly decreased, and was not elevated by overexpression of GPx-1-198Leu gene. Increased GPx activity was observed in WT Se-supplemented mice and Tg Se-supplemented mice (much more). Se deficiency as well as supplementation resulted in cardiac systolic dysfunction, which was not affected by GPx-1-198Leu gene. Se deficiency led to myocardial fibrosis and pathological changes accompanied by increased activation of caspase-9 and caspase-3. Se supplementation significantly reduced pathological changes, as well as caspase-9 and caspase-3 levels in the presence of increased myocardial fibrosis. In Se-deficient mice, GPx-1-198Leu overexpression did not significantly decrease myocardial pathological injuries and fibrosis. In Se-supplemented Tg mice, myocardial fibrosis and caspase-9 level were increased, although pathological injuries and caspase-3 were similar to that in Se-supplemented WT mice.ConclusionsSe deficiency as well as supplementation induced myocardial structural and functional abnormalities through activation of caspase-9 and caspase-3 in GPx-1P198L overexpression transgenic mice.