hsa_circ_0004771-Targeted Adsorption of miR-429 Mediates ATP2A2 Expression to Attenuate Endoplasmic Reticulum Stress and Mitochondrial Dysfunction During Myocardial Infarction.

Circular RNAs (circRNAs) have emerged as key regulators of cardiovascular pathophysiology. This study intended to mechanistically dissect the role of hsa_circ_0004771 in MI pathogenesis. An in vivo MI mouse model was established, and mouse cardiomyocytes (HL-1 cells) were cultured under hypoxic conditions to construct an in vitro cardiomyocyte injury model. Cardiac function in mice was assessed; serum markers of myocardial injury were quantified. Pathological alterations and levels of apoptosis in myocardial tissues were examined. Key oxidative stress indicators and pro-inflammatory cytokines were detected. Cell viability, cytotoxicity, and apoptosis were evaluated. Endoplasmic reticulum stress (ERS)-related proteins and mitochondrial function were analyzed. Serum samples from acute myocardial infarction (AMI) patients were collected for the detection of hsa_circ_0004771, miR-429, and ATPase sarcoplasmic/endoplasmic reticulum Ca²⁺ transporting 2(ATP2A2) mRNA expression levels. Furthermore, dual-luciferase reporter assays and RNA pull-down assays were utilized to validate the interactions between miR-429 and circ_0004771 or ATP2A2. Circ_0004771 expression was significantly downregulated in AMI patients and experimental models. Overexpression of circ_0004771 improved cardiac function, ameliorated myocardial injury, decreased infarct size, suppressed oxidative stress markers, and attenuated inflammatory cytokine levels in MI mice. In vitro studies demonstrated that circ_0004771 overexpression alleviated hypoxia-induced injury in HL-1 cardiomyocytes, concurrently mitigating ERS, mitochondrial dysfunction, and calcium overload. Mechanistically, circ_0004771 acted as a sponge of miR-429, thereby upregulating ATP2A2 expression. Inhibition of miR-429 attenuated hypoxia-induced cardiomyocyte damage, while miR-429 overexpression reversed the protective effects of circ_0004771. Silencing of ATP2A2 abrogated the therapeutic benefits of miR-429 inhibition. Circ_0004771 mitigates hypoxia-induced ERS, mitochondrial dysfunction, and calcium overload via the miR-429/ATP2A2 axis in MI.