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Atherosclerosis is a progressive disorder characterized by the buildup of plaques on the arterial inner wall, causing them to narrow and harden over time. These plaques comprise lipids, calcium, blood components, carbohydrates, and fibrous tissue. The process primarily affects the intima of large and medium-sized arteries, reducing blood flow in any artery.Etiology and risk factorsThe cause of atherosclerosis is multifactorial, involving a complex interplay among endothelial injury, lipid...
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Coronary Artery Disease (CAD): An Overview with Scientific InsightsCoronary Artery Disease (CAD), often referred to as C-A-D, is a prevalent blood vessel disorder classified under the broader category of atherosclerosis. Atherosclerosis is a pathological process characterized by the hardening and narrowing of arteries due to the accumulation of atherosclerotic plaques. These plaques are composed of cholesterol, fatty substances, inflammatory cells, calcium, and fibrin, reducing blood flow to...
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ASIC1/RIP1 accelerates atherosclerosis via disrupting lipophagy.

Yuan-Mei Wang1, Huang Tang2, Ya-Jie Tang3

  • 1Department of Physiology & Institute of Neuroscience, Hengyang Medical College, University of South China, Hengyang 421001, Hunan, People's Republic of China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, People's Republic of China.

Journal of Advanced Research
|November 6, 2023
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Summary

Acid-sensing ion channel 1 (ASIC1) in macrophages inhibits lipophagy, promoting atherosclerosis. Targeting ASIC1 and RIP1 signaling offers a potential therapeutic strategy for treating atherosclerosis.

Keywords:
ASIC1AtherosclerosisLipid accumulationLipophagyRIP1

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Area of Science:

  • Cardiovascular Research
  • Molecular Biology
  • Cellular Metabolism

Background:

  • Atherosclerosis is a significant global health concern, driven by complex cellular mechanisms.
  • Acid-sensing ion channel 1 (ASIC1) is implicated in impeding macrophage cholesterol efflux, but its role in atherogenesis is unclear.

Purpose of the Study:

  • To investigate the role of ASIC1 in the development of atherosclerosis.
  • To elucidate the underlying molecular mechanisms involving ASIC1 and lipophagy.

Main Methods:

  • Single-cell RNA sequencing (scRNA-seq) to analyze ASIC1 expression and lipophagy in human atherosclerotic lesions.
  • In vivo (human and mouse models) and in vitro (cell lines) validation of ASIC1/RIP1 signaling in lipophagy.

Main Results:

  • Increased ASIC1 protein in macrophages correlated with decreased lipophagy in human and mouse atherosclerotic lesions.
  • ASIC1 interaction with RIP1 promotes RIP1 and TFEB phosphorylation, disrupting lipophagy and increasing lipid accumulation.
  • ASIC1 deficiency or RIP1 inhibition reversed these effects, attenuating atherogenesis and restoring TFEB-mediated lipophagy in vivo.

Conclusions:

  • Macrophage ASIC1 plays a critical role in inhibiting lipophagy via RIP1 interaction, thereby promoting atherogenesis.
  • Targeting ASIC1 presents a promising therapeutic strategy for atherosclerosis treatment.