AMP-activated protein kinase mediates the effects of lipoprotein-associated phospholipase A2 on endothelial dysfunction in atherosclerosis

Yang, Li; Cong, Hongliang; Wang, Shu Feng; Liu, Ting

doi:10.3892/etm.2017.4142

Cited by 17 publications

(12 citation statements)

References 50 publications

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“…The AMPKα isoform is mainly expressed in VSMCs (Cai et al, 2016;Song et al, 2011), cardiomyocytes (X. and adipocytes (Sun et al, 2017). Recent evidence indicated that the activation of AMPKα stabilizes atherosclerotic plaque (Liang et al, 2018;Ma et al, 2018;L. Yang, Cong, Wang, & Liu, 2017).…”

Section: Discussionmentioning

confidence: 99%

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

Zhou

Huang

et al. 2018

Journal Cellular Physiology

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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.

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Section: Discussionmentioning

confidence: 99%

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

Zhou

Huang

et al. 2018

Journal Cellular Physiology

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“…AA is increased in the circulation, kidney, and urine with HFD in our study and this is consistent with increased circulating PUFA's demonstrated with HFD feeding in Sprague-Dawley rats (40). In excess nutrient states, phospholipase D suppresses AMPK activity through the mammalian/mechanistic target of rapamycin (mTOR); in return, AMPK activation decreased phospholipase D activity similar to the effect of AMPK activation on other phospholipases in vascular smooth muscles, and endothelial cells (19,41,42). Thus, the effect of AMPK activation on phospholipases in our study could be responsible for the changes to the PUFA levels with AICAR therapy.…”

Section: Pufa's Are Unaffected By Hfd or Ampk Activation In Our Studysupporting

confidence: 58%

AMP-activated protein kinase activation ameliorates eicosanoid dysregulation in high-fat-induced kidney disease in mice

Declèves

Mathew

Armando

et al. 2019

Journal of Lipid Research

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High-fat diet (HFD) causes renal lipotoxicity that is ameliorated with AMPK activation.Although bioactive eicosanoids increase with HFD and are essential in regulation of renal disease, their role in the inflammatory response to HFD-induced kidney disease and their modulation by AMPK activation remain unexplored. In a mouse model, we explored the effects of HFD on eicosanoid synthesis and the role of AMPK activation in ameliorating these changes. We used targeted lipidomic profiling with quantitative mass spectrometry to determine PUFA and eicosanoid content in kidneys, urine, renal arterial and venous circulation. HFD increased phospholipase expression as well as the total and free proinflammatory AA and anti-inflammatory DHA in kidneys. Consistent with the parent PUFA levels, the AA-and DHA-derived lipoxygenase (LOX), cytochrome P450, and nonenzymatic degradation (NE) metabolites increased in kidneys with HFD, while EPAderived LOX and NE metabolites decreased. Conversely, treatment with AICAR, AMPK activator, reduced the free AA and DHA content and the DHA-derived metabolites in kidney. Interestingly, both kidney and circulating AA, AA metabolites, and EPA-derived LOX and NE metabolites are increased with HFD; whereas, DHA metabolites are increased in kidney in contrast to their decreased circulating levels with HFD. Together, these changes showcase HFD-induced pro-and anti-inflammatory eicosanoid dysregulation and highlight the role of AMPK in correcting HFD-induced dysregulated eicosanoid pathways.

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“…NO is a multifunctional signaling molecule produced by HVECs and is involved in the maintenance of metabolic and cardiovascular homeostasis. NO is also a potent endogenous vasodilator associated with key processes that suppress the formation of vascular lesions [35] and protects against atherosclerosis by inhibiting oxidation, scavenging free radicals, inhibiting the oxidation of lowdensity lipoprotein (LDL) in blood vessels, preventing the production of oxidized LDL (Ox-LDL), inhibiting the activation of nuclear factor κB (NF-κB) [36], preventing abnormal constriction (vasospasm) of coronary arteries etc. NO also inhibits the infiltration and adhesion of white blood cells (macrophages) [37].…”

Section: Nitric Oxide (No)mentioning

confidence: 99%

The emerging role of cell senescence in atherosclerosis

Zheng

Wang

et al. 2020

Clinical Chemistry and Laboratory Medicine (CCLM)

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Cell senescence is a fundamental mechanism of aging and appears to play vital roles in the onset and prognosis of cardiovascular disease, fibrotic pulmonary disease, liver disease and tumor. Moreover, an increasing body of evidence shows that cell senescence plays an indispensable role in the formation and development of atherosclerosis. Multiple senescent cell types are associated with atherosclerosis, senescent human vascular endothelial cells participated in atherosclerosis via regulating the level of endothelin-1 (ET-1), nitric oxide (NO), angiotensin II and monocyte chemoattractant protein-1 (MCP-1), senescent human vascular smooth muscle cells-mediated plaque instability and vascular calcification via regulating the expression level of BMP-2, OPN, Runx-2 and inflammatory molecules, and senescent macrophages impaired cholesterol efflux and promoted the development of senescent-related cardiovascular diseases. This review summarizes the characteristics of cell senescence and updates the molecular mechanisms underlying cell senescence. Moreover, we also discuss the recent advances on the molecular mechanisms that can potentially regulate the development and progression of atherosclerosis.

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AMP-activated protein kinase mediates the effects of lipoprotein-associated phospholipase A2 on endothelial dysfunction in atherosclerosis

Cited by 17 publications

References 50 publications

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

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

AMP-activated protein kinase activation ameliorates eicosanoid dysregulation in high-fat-induced kidney disease in mice

The emerging role of cell senescence in atherosclerosis

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