1. Exogenous heat shock protein-70 inhibits cigarette smoke-induced intimal thickening.
- Author
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Matsumoto M, Dimayuga PC, Wang C, Kirzner J, Cercek M, Yano J, Chyu KY, Shah PK, and Cercek B
- Subjects
- Animals, Aorta cytology, Aorta drug effects, Aorta metabolism, Atherosclerosis etiology, Atherosclerosis prevention & control, Carotid Arteries drug effects, Carotid Arteries metabolism, Carotid Arteries pathology, Cell Cycle drug effects, Cell Proliferation drug effects, Cyclin-Dependent Kinase Inhibitor p21 metabolism, DNA-Binding Proteins metabolism, Extracellular Signal-Regulated MAP Kinases metabolism, Gene Expression, HSP70 Heat-Shock Proteins genetics, HSP70 Heat-Shock Proteins pharmacology, Hydrogen Peroxide pharmacology, Male, Mice, Mice, Inbred C57BL, Muscle, Smooth, Vascular cytology, Muscle, Smooth, Vascular drug effects, Muscle, Smooth, Vascular metabolism, Myocytes, Smooth Muscle drug effects, Myocytes, Smooth Muscle metabolism, Oxidative Stress drug effects, Proliferating Cell Nuclear Antigen metabolism, Rats, Recombinant Proteins pharmacology, Spleen metabolism, Transcription Factors metabolism, Tunica Intima drug effects, Tunica Intima metabolism, Tunica Media drug effects, Tunica Media metabolism, Tunica Media pathology, Atherosclerosis pathology, HSP70 Heat-Shock Proteins metabolism, Tobacco Smoke Pollution adverse effects, Tunica Intima pathology
- Abstract
Cigarette smoke is associated with increased carotid intimal thickening or stroke. Preliminary work showed that exposure to smoke resulted in a 4.5-fold reduction of heat shock protein-70 (HSP70) expression in spleens of mice using gene microarray analysis. In the current study, we investigated the role of extracellular HSP70 in carotid intimal thickening of mice exposed to cigarette smoke. Intimal thickening was induced by placement of a cuff around the right carotid artery of mice. Cuff injury resulted in increased HSP70 mRNA expression in carotid arteries that persisted for 21 days. Cigarette smoke exposure decreased arterial HSP70 expression and significantly increased intimal thickening compared with mice exposed to air. Treatment of mice exposed to cigarette smoke with intravenous recombinant HSP70 attenuated intimal thickening through reduced phosphorylated extracellular signal-regulated kinase (pERK) expression in the arterial wall. In vitro experiments with rat aortic smooth muscle cells confirmed that recombinant HSP70 decreases pERK and proliferating cell nuclear antigen (PCNA) expression in cells exposed to cigarette smoke extract and H(2)O(2). Our study suggests that decreased expression of arterial HSP70 is an important mechanism by which exposure to cigarette smoke augments intimal thickening. The effects of recombinant HSP70 suggest a role for extracellular HSP70.
- Published
- 2008
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