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Defective autophagy in vascular smooth muscle cells enhances cell death and atherosclerosis

Yusuke Osonoi1,2, Tomoya Mita1,2,3, Kosuke Azuma1

  • 1a Department of Metabolism & Endocrinology , Juntendo University Graduate School of Medicine , 2-1-1 Hongo, Bunkyo-ku, Tokyo 113-8421 , Japan.

Autophagy
|July 21, 2018
PubMed

Insights

Defective autophagy in vascular smooth muscle cells impairs cell function and accelerates atherosclerosis, leading to aortic rupture in mice. This highlights autophagy

Area of Science:

  • Cell Biology
  • Cardiovascular Research
  • Metabolism

Background:

  • Macroautophagy/autophagy is a fundamental catabolic process.
  • Its role in vascular smooth muscle cells (SMCs) and atherosclerosis is not fully understood.

Purpose of the Study:

  • To investigate the function of autophagy in SMCs during the development of atherosclerosis.

Main Methods:

  • Generated SMC-specific autophagy gene atg7 knockout (Atg7cKO) mice.
  • Utilized 7-ketocholesterol treatment and Apoe-deficient (apoeKO) mouse models.
  • Analyzed aortic tissues from mice fed a Western diet.

Main Results:

  • SMCs lacking autophagy showed reduced growth, increased death, and enhanced apoptosis with 7-ketocholesterol.
  • Atg7cKO:apoeKO mice exhibited reduced medial cellularity, increased cell death, and aortic rupture.
  • Defective autophagy led to increased plaque area, medial disruption, and aneurysm formation.

Conclusions:

  • Autophagy is crucial for SMC function and preventing atherosclerotic progression.
  • Deficiency in SMC autophagy exacerbates atherosclerosis and promotes outward arterial remodeling.
  • Targeting autophagy may offer therapeutic strategies for atherosclerosis.
Keywords:
Aneurysmatherosclerosisautophagycell deathsenescencesmooth muscle cells

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