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Aberrant proliferation of vascular smooth muscle cells (VSMC) is a critical contributor to the pathogenesis of atherosclerosis (AS). Our previous studies have demonstrated that apelin‐13/APJ confers a proliferative response in VSMC, however, its underlying mechanism remains elusive. 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 enhances 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 apelin‐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. Conversely, 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 of 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 aortic wall in vivo. Finally, PINK1‐/‐ mutant mice with apelin‐13 attenuates atherosclerotic lesions along with defective in mitophagy. PINK1/Parkin‐mediated mitophagy promotes apelin‐13‐evoked human aortic VSMC proliferation by activating p‐AMPKα and exacerbates the progression of atherosclerotic lesions. PINK1/Parkin‐mediated mitophagy promotes apelin‐13‐induced human aortic vascular smooth muscle cell proliferation through activating AMPKα in vitro. Mitophagy exacerbates atherosclerotic lesions of ApoE‐/‐ mice with apelin‐13 stimulation in vivo. Apelin‐13 also increases mitochondrial fission and decreases mitochondrial fusion via AMPKα, thus contributing to the regulation of mitochondrial dynamics. PINK1 deficiency results in defective mitophagy and attenuates vascular smooth muscle cells (VSMC) proliferation induced by apelin‐13. AMPKα‐PINK1‐Parkin axis plays a crucial role in apelin‐13‐induced human aortic VSMC proliferation and atherosclerotic plaques in vitro and in vivo, and consequently atherosclerosis. [ABSTRACT FROM AUTHOR]

The Golgi apparatus (GA) is a ribbon-like system of stacks which consist of multiple closely apposed flattened cisternae and vesicles usually localized in the juxta-nuclear area. As for the biological functions, the GA plays a major role in protein biosynthesis, post-translational modification, and sorting protein from ER to plasma membrane and other destinations. Structural changes and functional disorder of the GA is associated with various diseases. Moreover, increasing evidence revealed that swelling, poor development, and other morphological alterations of the GA are linked to cardiovascular diseases such as heart failure (HF), arrhythmia, and dilated cardiomyopathy. Furthermore, dysfunction of the GA is also related to cardiovascular diseases since the GA is extremely responsible for transport, glycosylation, biosynthesis, and subcellular distribution of cardiovascular proteins. This review gives a brief overview of the intricate relationship between the GA and cardiovascular diseases. In addition, we provide a further prospective that the GA may provide diagnosis reference for cardiovascular diseases, and changes in the ultrastructure and morphology of the GA such as swelling, poor development, and fragmentation may serve as a reliable index for cardiovascular diseases. [ABSTRACT FROM AUTHOR]