Pitavastatin alters the expression of thrombotic and fibrinolytic proteins in human vascular cells

Ronald A. Markle, Jihong Han, Barbara D. Summers, Toru Yokoyama, Katherine A. Hajjar, David P. Hajjar, Antonio M. Gotto, Andrew C. Nicholson

Research output: Contribution to journalArticlepeer-review

43 Scopus citations

Abstract

In addition to lowering blood lipids, clinical benefits of 3-hydroxy-3-methylglutaryl coenzyme A (HMG Co-A; EC 1.1.1.34) reductase inhibitors may derive from altered vascular function favoring fibrinolysis over thrombosis. We examined effects of pitavastatin (NK-104), a relatively novel and long acting statin, on expression of tissue factor (TF) in human monocytes (U-937), plasminogen activator inhibitor-1 (PAI-1), and tissue-type plasminogen activator (t-PA) in human aortic smooth muscle cells (SMC) and human umbilical vein endothelial cells (HUVEC). In monocytes, pitavastatin reduced expression of TF protein induced by lipopolysaccharide (LPS) and oxidized low-density lipoprotein (OxLDL). Similarly, pitavastatin also reduced expression of TF mRNA induced by LPS. Pitavastatin reduced PAI-1 antigen released from HUVEC under basal, OxLDL-, or tumor necrosis factor-alpha (TNF-α)-stimulated conditions. Reductions of PAI-1 mRNA expression correlated with decreased PAI-1 antigen secretion and PAI-1 activity as assessed by fibrin-agarose zymography. In addition, pitavastatin decreased PAI-1 antigen released from OxLDL-treated and untreated SMC. Conversely, pitavastatin enhanced t-PA mRNA expression and t-PA antigen secretion in untreated OxLDL-, and TNF-α-treated HUVEC and untreated SMC. Finally, pitavastatin increased t-PA activity as assessed by fibrin-agarose zymography. Our findings demonstrate that pitavastatin may alter arterial homeostasis favoring fibrinolysis over thrombosis, thereby reducing risk for thrombi at sites of unstable plaques.

Original languageEnglish (US)
Pages (from-to)23-32
Number of pages10
JournalJournal of Cellular Biochemistry
Volume90
Issue number1
DOIs
StatePublished - Sep 1 2003

Keywords

  • Endothelial cell
  • Fibrinolysis
  • Monocyte
  • Smooth muscle
  • Statin
  • Thrombosis

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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