Aprotinin Inhibits Vascular Smooth Muscle Cell Inflammation and Proliferation via Induction of HO-1.
10.4196/kjpp.2009.13.2.123
- Author:
Dong Hyup LEE
1
;
Hyoung Chul CHOI
;
Kwang Youn LEE
;
Young Jin KANG
Author Information
1. Department of Cardiac Surgery, College of Medicine, Yeungnam University, Daegu 705-717, Korea.
- Publication Type:Original Article
- Keywords:
Aprotinin;
Inflammation;
Vascular smooth muscle cell;
Proliferation;
HO-1;
iNOS
- MeSH:
Animals;
Aprotinin;
Cardiopulmonary Bypass;
Cell Proliferation;
Inflammation;
Metalloporphyrins;
Muscle, Smooth, Vascular;
Nitric Oxide Synthase Type II;
Phosphorylation;
Phosphotransferases;
Protoporphyrins;
Rats;
Reactive Oxygen Species;
Tin
- From:The Korean Journal of Physiology and Pharmacology
2009;13(2):123-129
- CountryRepublic of Korea
- Language:English
-
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-1beta plus TNF-alpha), reactive oxygen species (ROS) generation, and vascular smooth muscle cell (VSMC) proliferation were due to HO-1 induction in rat VSMCs. Aprotinin induced HO-1 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-1 inhibitor, tin protoporphyrin IX (SnPPIX). HO-1 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.
