LncRNA HYMAI Promotes Endothelial Cell Autophagy via miR-19a-3p/ ATG14 to Attenuate the Progression of Coronary Atherosclerotic Disease.

Background: Coronary atherosclerotic disease (CAD), clinically manifesting as progressive coronary atherosclerosis (As), involves endothelial cell (EC) dysfunction. HYMAI may contribute to atherogenesis by acting on ECs, but its regulation of endothelial injury and role in As pathogenesis remain unclear.

Methods: HYMAI expression was assessed via PCR array in blood samples from healthy individuals, patients with premature coronary atherosclerotic disease (PCAD), and patients with mature coronary atherosclerotic disease (MCAD) (each group consisting of 4 males and 2 females). Using male ApoE-/- and LDLR-/- mice fed with a high-fat diet (HFD) to model As, we evaluated the effects of endothelial-specific HYMAI overexpression on aortic lesions. Autophagy and apoptosis were analyzed in ox-LDL-treated human coronary artery endothelial cells (HCAECs).

Results: HYMAI levels increased sequentially in healthy individuals, PCAD, and MCAD patients. In HFD-fed ApoE-/- and LDLR-/- mice, aortic atherosclerosis progressed with age, while HYMAI expression in aortic tissue declined. HYMAI overexpression in ECs promoted autophagy and attenuated atherosclerosis. in vitro, ox-LDL suppressed HYMAI, triggering autophagic inhibition and apoptotic activation in HCAECs. HYMAI overexpression rescued ox-LDL-impaired autophagy and suppressed apoptosis through the miR-19a-3p/ATG14 pathway. miR-19a-3p overexpression reversed autophagic rescue and promoted apoptosis by repressing ATG14.

Discussion: HYMAI upregulation counteracts ox-LDL-treated endothelial autophagic inhibition via the miR-19a-3p/ATG14 pathway, rescuing apoptosis and attenuating As in both in vivo and in vitro settings.

Conclusion: Our results demonstrated that HYMAI attenuated As progression in As mice and ox-LDL-treated HCAECs by enhancing endothelial autophagy through the miR-19a-3p/ATG14 axis. These findings establish HYMAI as a novel regulatory mechanism and provide a potential druggable target for As and CAD.