Role of AMPK in atherosclerosis via autophagy regulation

Abstract

Atherosclerosis is characterized by the accumulation of lipids and deposition of fibrous elements in the vascular wall, which is the primary cause of cardiovascular diseases. Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor of energy metabolism that regulates multiple physiological processes, including lipid and glucose metabolism and the normalization of energy imbalances. Overwhelming evidence indicates that AMPK activation markedly attenuates atherosclerosis development. Autophagy inhibits cell apoptosis and inflammation and promotes cholesterol efflux and efferocytosis. Physiological autophagy is essential for maintaining normal cardiovascular function. Increasing evidence demonstrates that autophagy occurs in developing atherosclerotic plaques. Emerging evidence indicates that AMPK regulates autophagy via a downstream signaling pathway. The complex relationship between AMPK and autophagy has attracted the attention of many researchers because of this close relationship to atherosclerosis development. This review demonstrates the role of AMPK and autophagy in atherosclerosis. An improved understanding of this interrelationship will create novel preventive and therapeutic strategies for atherosclerosis.

CD39 identifies a microenvironment-specific anti-inflammatory CD8+ T-cell population in atherosclerotic lesions

“…These nucleotides can induce both atherogenic signaling [30], but may also induce phosphorylation of the AMP-activated protein kinase (AMPK) [31]. This phosphorylation results in functional activation of AMPK, which was shown to reduce atherosclerosis development by inducing autophagy and subsequently promoting cholesterol efflux from macrophages, as well as diminishing inflammatory responses [32].…”

CTRP13 inhibits atherosclerosis via autophagy‐lysosome‐dependent degradation of CD36

“…Therefore, CTRP13 led to an induction of autophagosome formation under atherosclerosis. CTRP13 is reported to activate AMPK signaling, and AMPK plays an important role in autophagy (18,27), so we suspected whether AMPK participated in autophagymediated degradation of CD36 under CTRP13 administration. We found that CTRP13 could enhance AMPK activity in primary peritoneal macrophages (Supplemental Fig.…”

Midkine Inhibits Cholesterol Efflux by Decreasing ATP-Binding Membrane Cassette Transport Protein A1 via Adenosine Monophosphate-Activated Protein Kinase/Mammalian Target of Rapamycin Signaling in Macrophages

“…16 Adenosine monophosphate-activated protein kinase (AMPK) also plays a central role in regulating nutritional metabolism and maintaining energy balance. 17 Increasing evidence suggests that improving the activity of AMPK protects normal cardiovascular function by reducing lipid accumulation in macrophages and enhancing atherosclerotic plaque stability. 18,19 In addition to regulating energy homeostasis, AMPK exerts a protective effect in atherosclerosis by inhibiting inflammation, endoplasmic reticulum stress, and SMC proliferation.…”