PINK1/Parkin ‐mediated mitophagy promotes apelin‐13‐induced vascular smooth muscle cell proliferation by AMPKα and exacerbates atherosclerotic lesions

In this study, we aimed to investigate the role of mitophagy in apelin‐13‐induced VSMC proliferation and atherosclerotic lesions in apolipoprotein E knockout (ApoE‐/‐) mice. Apelin‐13 enh ances human aortic VSMC proliferation and proliferative regulator proliferating cell nuclear antigen expression in dose and time‐dependent manner, while is abolished by APJ antagonist F13A. We observe the engulfment of damage mitochondria by autophagosomes (mitophagy) of human aortic VSMC in apeli n‐13 stimulation. Mechanistically, apelin‐13 increases p‐AMPKα and promotes mitophagic activity such as the LC3I to LC3II ratio, the increase of Beclin‐1 level and the decrease of p62 level. Importantly, the expressions of PINK1, Parkin, VDAC1, and Tom20 are induced by apelin‐13. Converse ly, blockade of APJ by F13A abolishes these stimulatory effects. Human aortic VSMC transfected with AMPKα, PINK1, or Parkin and subjected to apelin‐13 impairs mitophagy and prevents proliferation. Additional, apelin‐13 not only increases the expression of Drp1 but also reduces the expressions o f Mfn1, Mfn2, and OPA1. Remarkably, the mitochondrial division inhibitor‐1(Mdivi‐1), the pharmacological inhibition of Drp1, attenuates human aortic VSMC proliferation. Treatment of ApoE‐/‐ mice with apelin‐13 accelerates atherosclerotic lesions, increases p‐AMPKα and mitophagy in aorti c wall in vivo. Finally, PINK1‐/‐ mutant mice with apelin‐13 attenuates atherosclerotic lesi...
Source: Journal of Cellular Physiology - Category: Cytology Authors: Tags: ORIGINAL RESEARCH ARTICLE Source Type: research