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Deficiency of TDAG51 protects against atherosclerosis by modulating apoptosis, cholesterol efflux, and

Gazi S Hossain1, Edward G Lynn, Kenneth N Maclean

  • 1Division of Nephrology, Department of Medicine, McMaster University and St. Joseph's Healthcare Hamilton, Ontario, Canada.

Journal of the American Heart Association
|May 21, 2013
PubMed

Insights

T-cell death-associated gene 51 (TDAG51) deficiency reduces atherosclerosis by enhancing cellular protection and reverse cholesterol transport. This suggests TDAG51 modulation may offer therapeutic benefits for cardiovascular disease (CVD).

Area of Science:

  • Cardiovascular Biology
  • Molecular Medicine
  • Cellular Stress Response

Background:

  • Endoplasmic reticulum (ER) stress-induced apoptosis contributes to atherothrombosis, a key factor in cardiovascular disease (CVD).
  • T-cell death-associated gene 51 (TDAG51) is upregulated by ER stress and promotes apoptosis, and is found in atherosclerotic lesions.

Purpose of the Study:

  • To investigate the role of TDAG51 in the development of atherosclerosis.
  • To explore the cellular mechanisms by which TDAG51 influences atherogenesis.

Main Methods:

  • Generated and analyzed TDAG51-deficient and apolipoprotein E-deficient (TDAG51(-/-)/ApoE(-/-)) mice to assess atherosclerotic lesion progression.
  • Examined phenotypic changes in macrophages and endothelial cells from TDAG51-deficient mice.
  • Conducted case-control studies to evaluate the association of a TDAG51 gene variant with CVD.

Main Results:

  • TDAG51 deficiency significantly reduced atherosclerotic lesion growth and necrosis in mice without altering plasma lipid or glucose levels.
  • TDAG51 deficiency enhanced macrophage and endothelial cell cytoprotection against ER and oxidative stress.
  • TDAG51 deficiency upregulated peroxiredoxin-1 (Prdx-1) and enhanced PPARγ-dependent reverse cholesterol transport.
  • A genetic variant in the human TDAG51 gene region (rs2367446) was associated with an increased risk of CVD.

Conclusions:

  • TDAG51 plays a significant role in atherogenesis by influencing cellular stress responses and lipid metabolism.
  • Modulating TDAG51 expression or activity presents a potential therapeutic strategy for treating cardiovascular disease.
Abstract

Keywords:
apoptosisarteriosclerosisatherosclerosiscardiovascular diseases

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