title: Tissue inhibitor of metalloproteinase-1 is an early marker of acute endothelial dysfunction in a rodent model of venous oxidative injury.
abstract: Although there are extensive research data regarding arterial endothelial dysfunction, the effects of venous endothelial dysfunction are not well characterized. Matrix metalloproteinases (MMPs) have a defined role in vascular remodeling. MMPs are endopeptidases that are capable of degrading extracellular matrix proteins. We hypothesize that tissue inhibitor of metalloproteinase-1 (TIMP-1) can serve as an indicator of acute venous endothelial dysfunction in a rat model of oxidative injury. The experimental groups evaluated were as follows: rats not undergoing oxidative injury (controls), rats that received rose bengal but no laser (shams), and rats that received both rose bengal and laser illumination, resulting in an oxidative injury. Animals were evaluated at baseline (control, shams) and at 1 hr and 1 day post-oxidative injury. mRNA expression was determined by gene array technology and real-time polymerase chain reaction, plasma and vein wall TIMP-1 protein concentrations were determined by enzyme-linked immunosorbent assay, and vein wall morphometrics (cells/five high-power fields) were performed. B-cell lymphoma 2-like gene expression was upregulated at both 1 hr and 1 day post-injury. TIMP-1 protein and mRNA expression were significantly increased post-oxidative injury. One hour postinjury, vein wall polymorphonuclear leukocytes were present in significant numbers. Our results support the hypothesis that increased expression of TIMP-1 in venous endothelium and plasma may serve as an early indicator of endothelial dysfunction.
authors.affiliation: Section of Vascular Surgery, Jobst Vascular Research Laboratories, University of Michigan, Ann Arbor, MI 48109-0654, USA. rashidah@umich.edu
authors.forename: Rashida
authors.initials: R
authors.lastname: Moore
authors.forename: Angela
authors.initials: A
authors.lastname: Hawley
authors.forename: Robert
authors.initials: R
authors.lastname: Sigler
authors.forename: Diana
authors.initials: D
authors.lastname: Farris
authors.forename: Shirley
authors.initials: S
authors.lastname: Wrobleski
authors.forename: Eduardo
authors.initials: E
authors.lastname: Ramacciotti
authors.forename: Daniel
authors.initials: D
authors.lastname: Myers
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D020556:Neutrophil Infiltration; D018384:Oxidative Stress; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012395:Rose Bengal; D013997:Time Factors; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation; D014652:Vascular Diseases / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D014682:Vena Cava, Inferior / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D015415:Biomarkers; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D019715:Tissue Inhibitor of Metalloproteinase-1; D012395:Rose Bengal