title: Exogenous heat shock protein-70 inhibits cigarette smoke-induced intimal thickening.
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.
authors.affiliation: Division of Cardiology and Atherosclerosis Research Center, Burns and Allen Research Institute, Cedars-Sinai Medical Center, 8700 Beverly Blvd., Los Angeles, CA 90048, USA.
authors.forename: Michiaki
authors.initials: M
authors.lastname: Matsumoto
authors.forename: Paul C
authors.initials: PC
authors.lastname: Dimayuga
authors.forename: Charles
authors.initials: C
authors.lastname: Wang
authors.forename: Jonathan
authors.initials: J
authors.lastname: Kirzner
authors.forename: Miha
authors.initials: M
authors.lastname: Cercek
authors.forename: Juliana
authors.initials: J
authors.lastname: Yano
authors.forename: Kuang-Yuh
authors.initials: KY
authors.lastname: Chyu
authors.forename: Prediman K
authors.initials: PK
authors.lastname: Shah
authors.forename: Bojan
authors.initials: B
authors.lastname: Cercek
mesh_terms: D000818:Animals; D001011:Aorta / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D050197:Atherosclerosis / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D002339:Carotid Arteries / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000378:metabolism; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D015870:Gene Expression; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D006861:Hydrogen Peroxide / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D018809:Proliferating Cell Nuclear Antigen / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000494:pharmacology; D013154:Spleen / Q000378:metabolism; D014028:Tobacco Smoke Pollution / Q000009:adverse effects*; D014157:Transcription Factors / Q000378:metabolism; D017539:Tunica Intima / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D017540:Tunica Media / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: C091732:BCL2-associated athanogene 1 protein; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; D018840:HSP70 Heat-Shock Proteins; D018809:Proliferating Cell Nuclear Antigen; D011994:Recombinant Proteins; D014028:Tobacco Smoke Pollution; D014157:Transcription Factors; D006861:Hydrogen Peroxide; D048049:Extracellular Signal-Regulated MAP Kinases