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Hyperhomocystinemia impairs endothelial function and eNOS activity via PKC activation

Xiaohua Jiang1, Fan Yang, Hongmei Tan

  • 1Department of Medicine, Baylor College of Medicine, Houston, TX 77030, USA.

Arteriosclerosis, Thrombosis, and Vascular Biology
|October 8, 2005
PubMed

Insights

High homocysteine levels impair blood vessel function by reducing nitric oxide production. This endothelial dysfunction is mainly caused by protein kinase C activation, contributing to cardiovascular disease risk.

Area of Science:

  • Cardiovascular Biology
  • Endothelial Function
  • Metabolic Disease

Background:

  • Hyperhomocysteinemia (HHcy) is a risk factor for cardiovascular disease.
  • HHcy is linked to endothelial dysfunction, a key factor in vascular health.

Purpose of the Study:

  • To investigate the mechanistic role of HHcy in endothelial dysfunction.
  • To elucidate the molecular pathways affected by HHcy in the endothelium.

Main Methods:

  • Utilized functional models: aortic rings and intravital microscopy in cystathionine beta-synthase null (CBS(-/-)) mice.
  • Assessed endothelial nitric oxide synthase (eNOS) activity and phosphorylation in mouse and human aortic endothelial cells.
  • Investigated the effect of a protein kinase C (PKC) inhibitor (GF109203X) on eNOS activity.

Main Results:

  • Arterial relaxation was impaired in CBS(-/-) mice, while smooth muscle cell response to NO donors was preserved.
  • HHcy significantly reduced eNOS activity and altered its phosphorylation status (increased Thr495) in endothelial cells.
  • PKC inhibition reversed HHcy-induced eNOS inactivation and phosphorylation changes.

Conclusions:

  • HHcy impairs endothelial function and eNOS activity.
  • PKC activation is a primary mechanism underlying HHcy-mediated endothelial dysfunction.
Abstract

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