The Korean Journal of Physiology and Pharmacology

The Korean Society of Pharmacology (대한약리학회)
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Aprotinin Inhibits Vascular Smooth Muscle Cell Inflammation and Proliferation via Induction of HO-1

  • Lee, Dong-Hyup (Department of Cardiac Surgery, College of Medicine, Yeungnam University) ;
  • Choi, Hyoung-Chul (Department of Pharmacology and Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University) ;
  • Lee, Kwang-Youn (Department of Pharmacology and Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University) ;
  • Kang, Young-Jin (Department of Pharmacology and Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University)
  • Published : 2009.04.30
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Abstract

Aprotinin is used clinically in cardiopulmonary bypass surgery to reduce transfusion requirements and the inflammatory response. The mechanism of action for the anti-inflammatory effects of aprotinin is still unclear. We examined our hypothesis whether inhibitory effects of aprotinin on cytokine-induced inducible nitric oxide synthase (iNOS) expression (IL-$l\beta$ plus TNF-$\alpha$), reactive oxygen species (ROS) generation, and vascular smooth muscle cell (VSMC) proliferation were due to HO-l induction in rat VSMCs. Aprotinin induced HO-l protein expression in a dose-dependent manner, which was potentiated during inflammatory condition. Aprotinin reduced cytokine mixture (CM)-induced iNOS expression in a dose dependent manner. Furthermore, aprotinin reduced CM-induced ROS generation, cell proliferation, and phosphorylation of JNK but not of P38 and ERK1/2 kinases. Aprotinin effects were reversed by pre-treatment with the HO-l inhibitor, tin protoporphyrin IX (SnPPIX). HO-l is therefore closely involved in inflammatory-stimulated VSMC proliferation through the regulation of ROS generation and JNK phosphorylation. Our results suggest a new molecular basis for aprotinin anti-inflammatory properties.

Keywords

References

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