Aprotinin Inhibits Vascular Smooth Muscle Cell Inflammation and Proliferation via Induction of HO-1
The Korean Journal of Physiology and Pharmacology
;
: 123-129, 2009.
Article
in English
| WPRIM
| ID: wpr-728745
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Phosphorylation
/
Phosphotransferases
/
Protoporphyrins
/
Tin
/
Cardiopulmonary Bypass
/
Aprotinin
/
Reactive Oxygen Species
/
Cell Proliferation
/
Nitric Oxide Synthase Type II
/
Inflammation
Limits:
Animals
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2009
Type:
Article
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