2. Academic Validation
  3. Different stimuli induce endothelial dysfunction and promote atherosclerosis through the Piezo1/YAP signaling axis

Different stimuli induce endothelial dysfunction and promote atherosclerosis through the Piezo1/YAP signaling axis

  • Arch Biochem Biophys. 2023 Sep 14;747:109755. doi: 10.1016/j.abb.2023.109755.
Jingying Mao 1,  Ronghao Yang 2,  Ping Yuan 3,  Fei Wu 2,  Yan Wei 4,  Yongmei Nie 5,  Chunxiang Zhang 4,  Xiangyu Zhou 6
Affiliations

Affiliations

  • 1 Department of Thyroid and Vascular Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, China.
  • 2 Department of Thyroid and Vascular Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
  • 3 Department of Neurology, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
  • 4 Key Laboratory of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Laboratory of Sichuan Province, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, 646000, China.
  • 5 Department of Cardiovascular Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China.
  • 6 Department of Thyroid and Vascular Surgery, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, China; Metabolic Vascular Disease Key Laboratory of Sichuan Province, Luzhou, 646000, China.
PMID: 37714252 DOI: 10.1016/j.abb.2023.109755
Abstract

Vascular endothelial dysfunction is the initial step in atherosclerosis (AS). AS tends to occur at vascular bifurcations and curves, and endothelial cells(ECs) are highly susceptible to injury due to mechanical forces induced by disturbed flow (DF) with inconsistent blood flow directions. However, the pathogenesis of endothelial cell dysfunction in AS remains unclear and needs further study. Here, we found that Piezo1 expression was significantly increased in DF- and oxidized low-density lipoprotein(ox-LDL)-treated HUVECs in vitro and a model of atherosclerotic plaque growth in apoE-/- mice fed a Western diet. Furthermore, Piezo1 upregulated Autophagy levels in the HUVECs model, which was reversed by Piezo1 knockdown with a lentivirus-mediated shRNA system. Mechanistically, the level of Yes-associated protein (YAP), a transcriptional coactivator in the Hippo pathway, was significantly elevated in the DF- and ox-LDL-induced HUVECs model, and this effect was further inhibited by Piezo1 knockdown. Moreover, the Piezo1 agonist Yoda1 inhibited the protein level of microtubule-associated protein 1 light chain 3-II(LC3-II) and increased the protein level of sequestosome1(p62/SQSTM1) in a dose-dependent manner, while significantly promoting the protein expression and nuclear translocation of YAP. The YAP Inhibitor CA3 weakened Yoda1-mediated inhibition of Autophagy. Our results suggest that Piezo1 may regulate endothelial Autophagy by promoting YAP activation and nuclear translocation, thereby contributing to vascular endothelial dysfunction.

Keywords

Atherosclerosis; Autophagy; Piezo1; Shear stress; YAP.

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