C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis.

Sridevi Devaraj, Dan Yan Xu, Ishwarlal Jialal

Research output: Contribution to journalArticle

544 Scopus citations

Abstract

BACKGROUND: Inflammation plays a pivotal role in atherosclerosis. In addition to being a risk marker for cardiovascular disease, much recent data suggest that C-reactive protein (CRP) promotes atherogenesis via effects on monocytes and endothelial cells. The metabolic syndrome is associated with significantly elevated levels of CRP. Plasminogen activator inhibitor-1 (PAI-1), a marker of atherothrombosis, is also elevated in the metabolic syndrome and in diabetes, and endothelial cells are the major source of PAI-1. However, there are no studies examining the effect of CRP on PAI-1 in human aortic endothelial cells (HAECs). METHODS AND RESULTS: Incubation of HAECs with CRP results in a time- and dose-dependent increase in secreted PAI-1 antigen, PAI-1 activity, intracellular PAI-1 protein, and PAI-1 mRNA. CRP stabilizes PAI-1 mRNA. Inhibitors of endothelial NO synthase, blocking antibodies to interleukin-6 and an endothelin-1 receptor blocker, fail to attenuate the effect of CRP on PAI-1. CRP additionally increased PAI-1 under hyperglycemic conditions. CONCLUSIONS: This study makes the novel observation that CRP induces PAI-1 expression and activity in HAECs and thus has implications for both the metabolic syndrome and atherothrombosis.

Original languageEnglish (US)
Pages (from-to)398-404
Number of pages7
JournalCirculation
Volume107
Issue number3
StatePublished - Jan 28 2003

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Fingerprint Dive into the research topics of 'C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis.'. Together they form a unique fingerprint.

  • Cite this