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Updated: Sep 3, 2025

TGF-β-mediated Endothelial to Mesenchymal Transition EndMT and the Functional Assessment of EndMT Effectors using CRISPR/Cas9 Gene Editing
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BAG3 Alleviates Atherosclerosis by Inhibiting Endothelial-to-Mesenchymal Transition via Autophagy Activation

Hongtao Diao1,2, Kaili Wu1,2, Dingming Lan1,2

  • 1Guangdong Metabolic Diseases Research Center of Integrated Chinese and Western Medicine, Guangdong TCM Key Laboratory for Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou 510006, China.

Genes
|July 27, 2022
PubMed

Insights

B cell lymphoma 2-associated athanogene (BAG3) protects against atherosclerosis by promoting autophagy and suppressing endothelial-mesenchymal transition. This finding highlights BAG3 as a potential therapeutic target for cardiovascular disease.

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Biology

Background:

  • Atherosclerosis is a chronic inflammatory disease linked to cardiovascular events.
  • B cell lymphoma 2-associated athanogene (BAG3) has known roles in cancer and neurodegeneration, but its function in atherosclerosis is unknown.

Purpose of the Study:

  • To investigate the role of BAG3 in atherosclerosis.
  • To elucidate the molecular mechanisms underlying BAG3's function in this disease.

Main Methods:

  • Atherosclerosis was studied in apolipoprotein E knockout (ApoE-/-) mice.
  • BAG3 was overexpressed using lentivirus, and mice were fed a high-fat diet (HFD).
  • In vitro studies used human umbilical vein endothelial cells (HUVECs) to examine autophagy and endothelial-mesenchymal transition (EndMT).

Main Results:

  • Overexpression of BAG3 reduced atherosclerotic plaque areas in ApoE-/- mice.
  • BAG3 promoted autophagy in HUVECs.
  • BAG3 suppressed EndMT in HUVECs, mediated by interactions with HSP70 and HSPB8.

Conclusions:

  • BAG3 facilitates autophagy activation through the chaperone-assisted selective autophagy (CASA) complex.
  • This process inhibits EndMT, thereby suppressing atherosclerosis progression.
  • BAG3 represents a potential therapeutic target for atherosclerosis.

Keywords:
BAG3CASA complexEndMTatherosclerosisautophagy

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