Title:LncRNA HYMAI Promotes Endothelial Cell Autophagy via miR-19a-3p/ ATG14 to Attenuate the Progression of Coronary Atherosclerotic Disease
Volume: 33
Issue: 8
Author(s): Shao Ouyang, Zhi-Xiang Zhou, Hui-Ting Liu, Kun Zhou, Zhong Ren, Huan Liu, Qian Xu, Zhaoyue Wang, Wenhao Xiong, Gaofeng Zeng and Zhi-Sheng Jiang*
Affiliation:
- Key Lab for Arteriosclerology of Hunan Province, International Joint Laboratory for Arteriosclerotic Disease
Research of Hunan Province, Hengyang Medical School, Institute of Cardiovascular Disease, University
of South China, Hengyang, 421001, China
Keywords:
HYMAI, autophagy, miR-19a-3p, ATG14, atherosclerosis, coronary atherosclerotic disease.
Abstract:
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.
