title: Dynamics of heat shock protein 60 in endothelial cells exposed to cigarette smoke extract.
abstract: Heat shock protein 60 (HSP60), expressed on the surface of endothelial cells (ECs) stressed by e.g. oxidized LDL or mechanical shear, was shown to function as an auto-antigen and thus as a pro-atherosclerotic molecule. The aim of this study was to determine whether cigarette smoke chemicals can lead to the activation of the "HSP60 pathway." It was also our aim to elucidate the dynamics of HSP60 from gene expression to endothelial surface expression and secretion. Here we show for the first time that the exposure of human umbilical vein endothelial cells (HUVECs) to cigarette smoke extract (CSE) results in an up-regulation of HSP60 mRNA. Live cell imaging analysis of a HSP60-EYFP fusion protein construct transfected into ECs revealed that mitochondrial structures collapse in response to CSE exposure. As a result, HSP60 is released from the mitochondria, transported to the cell surface, and released into the cell culture supernatant. Analysis of HSP60 in the sera of healthy young individuals exposed to secondhand smoke revealed significantly elevated levels of HSP60. Cigarette smoking is one of the most relevant risk factors for atherosclerosis. Herein, we provide evidence that cigarette smoke may initiate atherosclerosis in the sense of the "auto-immune hypothesis of atherosclerosis."
authors.affiliation: Division of Experimental Pathophysiology and Immunology, Innsbruck Biocenter, Innsbruck Medical University, Innsbruck, Austria. Simone.Kreutmayer@i-med.ac.at
authors.forename: Simone Barbara
authors.initials: SB
authors.lastname: Kreutmayer
authors.forename: Barbara
authors.initials: B
authors.lastname: Messner
authors.forename: Michael
authors.initials: M
authors.lastname: Knoflach
authors.forename: Blair
authors.initials: B
authors.lastname: Henderson
authors.forename: Harald
authors.initials: H
authors.lastname: Niederegger
authors.forename: Günther
authors.initials: G
authors.lastname: Böck
authors.forename: Ruurd
authors.initials: R
authors.lastname: Van der Zee
authors.forename: Georg
authors.initials: G
authors.lastname: Wick
authors.forename: David
authors.initials: D
authors.lastname: Bernhard
mesh_terms: D000975:Antioxidants / Q000494:pharmacology; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000503:physiopathology; D015551:Autoimmunity / Q000187:drug effects; D002478:Cells, Cultured; D018834:Chaperonin 60 / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D045424:Complex Mixtures / Q000009:adverse effects; D015870:Gene Expression; D061307:Human Umbilical Vein Endothelial Cells / Q000166:cytology / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D008853:Microscopy; D008928:Mitochondria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism / Q000648:ultrastructure; D010957:Plasmids; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012906:Smoke / Q000009:adverse effects*; D012907:Smoking / Q000009:adverse effects* / Q000097:blood; D014026:Nicotiana / Q000009:adverse effects*; D014162:Transfection; D015854:Up-Regulation; D055815:Young Adult
chemical_list: D000975:Antioxidants; D018834:Chaperonin 60; D045424:Complex Mixtures; D011993:Recombinant Fusion Proteins; D012906:Smoke