title: Inducible reduction in pregnancy-associated plasma protein-A gene expression inhibits established atherosclerotic plaque progression in mice.
abstract: Pregnancy-associated plasma protein-A (PAPP-A) is a novel zinc metalloproteinase implicated in cardiovascular disease. The aim of this study was to determine whether a reduction in PAPP-A expression in the adult affects the progression of established atherosclerotic plaque. Apolipoprotein E-null mice were fed a high-fat diet for 5 weeks to initiate early-stage plaque development before tamoxifen-inducible, Cre recombinase-mediated excision of the floxed PAPP-A gene. High-fat feeding was continued, and after 10 weeks the aorta and brachiocephalic artery were harvested for atherosclerotic plaque analyses of overall burden and morphology, respectively. An inducible decrease in PAPP-A gene expression significantly inhibited atherosclerotic plaque progression as assessed by a 70% reduction in plaque burden in the aorta (P = .012) without an effect on the elevated circulating levels of cholesterol and triglycerides in this model. Furthermore, this reduction in PAPP-A prevented the development of advanced plaque with necrotic cores and buried fibrous caps in the brachiocephalic artery. These data indicate PAPP-A as a potential target to limit progression of established atherosclerotic plaque.
authors: Division of Endocrinology, Diabetes, Metabolism and Nutrition, Endocrine Research Unit, Mayo Clinic, Rochester, Minnesota 55905.
authors: Laurie K
authors: LK
authors: Bale
authors: Suban
authors: S
authors: Chakraborty
authors: Cheryl A
authors: CA
authors: Conover
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology; D001057:Apolipoproteins E / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000378:metabolism*; D016122:Brachiocephalic Trunk / Q000473:pathology; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D018450:Disease Progression; D005260:Female; D005786:Gene Expression Regulation; D006720:Homozygote; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009336:Necrosis; D058226:Plaque, Atherosclerotic / Q000378:metabolism; D011266:Pregnancy-Associated Plasma Protein-A / Q000235:genetics* / Q000502:physiology*
chemical_list: D001057:Apolipoproteins E; D011266:Pregnancy-Associated Plasma Protein-A