4.7 Article

Qiliqiangxin alleviates Ang II-induced CMECs apoptosis by downregulating autophagy via the ErbB2-AKT-FoxO3a axis

Journal

LIFE SCIENCES
Volume 273, Issue -, Pages -

Publisher

PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.lfs.2021.119239

Keywords

Qiliqiangxin; Cardiac microvascular endothelial cells; Autophagy; Apoptosis; ErbB2

Funding

  1. National Natural Science Foundation of China [81873123, 81870177]
  2. National Key Research and Development Program of China, China [2018YFE0103000]

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The study demonstrated that Qiliqiangxin exerts protective effects against high-concentration angiotensin II-induced cardiac microvascular endothelial cell apoptosis by inhibiting autophagy, with ErbB2 phosphorylation playing a key role in downregulating autophagy through the AKT-FoxO3a axis.
Our previous work revealed the protective effect of Qiliqiangxin (QLQX) on cardiac microvascular endothelial cells (CMECs), but the underlying mechanisms remain unclear. We aimed to investigate whether QLQX exerts its protective effect against high-concentration angiotensin II (Ang II)-induced CMEC apoptosis through the autophagy machinery. CMECs were cultured in high-concentration Ang II (1 mu M) medium in the presence or absence of QLQX for 48 h. We found that QLQX obviously inhibited Ang II-triggered autophagosome synthesis and apoptosis in cultured CMECs. QLQX-mediated protection against Ang II-induced CMEC apoptosis was reversed by the autophagy activator rapamycin. Specifically, deletion of ATG7 in cultured CMECs indicated a detrimental role of autophagy in Ang II-induced CMEC apoptosis. QLQX reversed Ang II-mediated ErbB2 phosphorylation impairment. Furthermore, inhibition of ErbB2 phosphorylation with lapatinib in CMECs revealed that QLQX-induced downregulation of Ang II-activated autophagy and apoptosis was ErbB2 phosphorylation-dependent via the AKT-FoxO3a axis. Activation of ErbB2 phosphorylation by Neuregulin-1 beta achieved a similar CMECprotective effect as QLQX in high-concentration Ang II medium, and this effect was also abolished by autophagy activation. These results show that the CMEC-protective effect of QLQX under high-concentration Ang II conditions could be partly attributable to QLQX-mediated ErbB2 phosphorylation-dependent downregulation of autophagy via the AKT-FoxO3a axis.

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