title: Increased expression of matrix metalloproteinase-1 in systemic vessels of preeclamptic women: a critical mediator of vascular dysfunction.
abstract: This study was conducted to determine the following: (1) whether matrix metalloproteinase-1 (MMP-1) is increased in systemic vessels of preeclamptic women, (2) whether this increase might be mediated by neutrophils, and (3) whether MMP-1 could be responsible for vascular dysfunction. Omental arteries and plasma were collected from healthy pregnant and preeclamptic women. Omental arteries were evaluated for gene and protein expression of MMP-1, collagen type 1α, tissue inhibitor of metalloproteinase-1, and vascular reactivity to MMP-1. Gene and protein expression levels were also evaluated in human vascular smooth muscle cells (VSMCs) co-cultured with activated neutrophils, reactive oxygen species, or tumor necrosis factor α. Vessel expression of MMP-1 and circulating MMP-1 levels were increased in preeclamptic women, whereas vascular expression of collagen or tissue inhibitor of metalloproteinase-1 were down-regulated or unchanged. In cultured VSMCs, the imbalance in collagen-regulating genes of preeclamptic vessels was reproduced by treatment with neutrophils, tumor necrosis factor α, or reactive oxygen species. Chemotaxis studies with cultured cells revealed that MMP-1 promoted recruitment of neutrophils via vascular smooth muscle release of interleukin-8. Furthermore, MMP-1 induced vasoconstriction via protease-activated receptor-1, whose expression was significantly increased in omental arteries of preeclamptic women and in VSMCs co-cultured with neutrophils. Collectively, these findings disclose a novel role for MMP-1 as a mediator of vasoconstriction and vascular dysfunction in preeclampsia.
authors.affiliation: Department of Obstetrics and Gynecology, Virginia Commonwealth University Medical Center, Richmond, Virginia 23298-0034, USA.
authors.forename: Guadalupe
authors.initials: G
authors.lastname: Estrada-Gutierrez
authors.forename: Renato E
authors.initials: RE
authors.lastname: Cappello
authors.forename: Nikita
authors.initials: N
authors.lastname: Mishra
authors.forename: Roberto
authors.initials: R
authors.lastname: Romero
authors.forename: Jerome F
authors.initials: JF
authors.lastname: Strauss
authors.forename: Scott W
authors.initials: SW
authors.lastname: Walsh
mesh_terms: D001808:Blood Vessels / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology*; D002478:Cells, Cultured; D002633:Chemotaxis; D005260:Female; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D009504:Neutrophils / Q000276:immunology; D011225:Pre-Eclampsia / Q000201:enzymology / Q000276:immunology / Q000503:physiopathology*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000378:metabolism; D044463:Receptor, PAR-1 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014661:Vasoconstriction
chemical_list: D017382:Reactive Oxygen Species; D044463:Receptor, PAR-1; D014409:Tumor Necrosis Factor-alpha; D020781:Matrix Metalloproteinase 1