The Angiotensin-(1–7)/MAS1 axis mediates cardioprotection, but its regulation under hypoxia, aging, and hypertension remains unclear. MicroRNAs (miRNAs) are key modulators of cardiovascular signaling, yet the role of miR-6315 in MAS1 regulation is unknown.
Objective
To investigate how hypoxic preconditioning regulates the miR-6315–MAS1 axis and its role in cardiomyocyte survival under Angiotensin II (Ang II) stress and pathological conditions.
Methods
Rat H9c2 and human AC16 cardiomyocytes were exposed to normoxia or hypoxia (0.5–24 h). MAS1 targeting by miR-6315 was validated using dual-luciferase assays. Gene and protein expression were analyzed by reverse transcription quantitative polymerase chain reaction (RT-qPCR), Western blot, and immunofluorescence. In vivo, Wistar–Kyoto and spontaneously hypertensive rats were subjected to graded hypoxia and aging models.
Results
Hypoxic preconditioning induced transient MAS1 upregulation, with increased protein kinase B (AKT) activation and hypoxia-inducible factor-1 alpha (HIF1α) stabilization. miR-6315 directly suppressed MAS1, whereas its inhibition restored survival signaling. Ang II increased miR-6315 and apoptosis, effects attenuated by hypoxia. Aging and hypertension were associated with reduced MAS1 expression.
Conclusion
Hypoxic preconditioning transiently relieves miR-6315-mediated repression of MAS1, activating a cardioprotective pathway that may represent a therapeutic target for enhancing myocardial resilience.
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