title: Changes in arterial expression of fibrinolytic system proteins in atherogenesis.
abstract: Plasminogen activators (PAs) and their inhibitor, plasminogen activator inhibitor type-1 (PAI-1), have been implicated in modulation of luminal fibrinolysis and mural proteolysis contributing to atherogenesis. Expression of PAs/PAI-1 (normalized to extracted tissue protein) was delineated by assays of conditioned media and of extracts from walls of human arterial segments in culture. Arterial specimens (n = 39 from 26 subjects) were divided into four groups: normal (n = 14), fatty streak (n = 6), moderate atherosclerosis (mural thickening with < 70% lumen obstruction, n = 5), and severe atherosclerosis (mural thickening with > 70% lumen obstruction, n = 14). Paired samples from the same individual comprising a normal arterial segment and an atherosclerotic segment were evaluated also. A fourfold molar excess in PAI-1:t-PA was seen in conditioned media from samples with any evidence of atherosclerosis compared with normal specimens (normal 21 +/- 4, diseased 82 +/- 21, P < or = .05). Compared with normal pairs, the tissue content of PAI-1 (ng) was increased in fatty streak lesions (n = 3, normal 35 +/- 12, fatty streak 50 +/- 8, P < or = .05); stable to decreased in moderate atherosclerosis (n = 3, normal 34 +/- 3, moderate 22 +/- 7, P = .16); and increased in severe atherosclerosis (n = 6, normal 48 +/- 9, severe 85 +/- 19, P < or = .05). The tissue content of PAs (ng), though not increased in fatty streak lesions, was elevated in moderately and severely atherosclerotic segments (normal 0.7 +/- 0.2, moderate 1.6 +/- 0.1; normal 0.8 +/- 0.3, severe 2.1 +/- 0.3, P < or = .05 for each comparison). Atherogenesis is associated with decreased luminal fibrinolytic capacity that may exacerbate thrombosis. Decreased mural proteolysis in early atherogenesis may exacerbate matrix accumulation. Increased mural proteolysis later is associated with, and may potentiate, smooth muscle cell migration and proliferation.
authors.affiliation: Department of Medicine, University of Vermont, Burlington. djschnei@zoo.uvm.edu
authors.forename: D J
authors.initials: DJ
authors.lastname: Schneider
authors.forename: M A
authors.initials: MA
authors.lastname: Ricci
authors.forename: D J
authors.initials: DJ
authors.lastname: Taatjes
authors.forename: P Q
authors.initials: PQ
authors.lastname: Baumann
authors.forename: J C
authors.initials: JC
authors.lastname: Reese
authors.forename: B J
authors.initials: BJ
authors.lastname: Leavitt
authors.forename: P M
authors.initials: PM
authors.lastname: Absher
authors.forename: B E
authors.initials: BE
authors.lastname: Sobel
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001158:Arteries / Q000737:chemistry / Q000473:pathology; D001161:Arteriosclerosis / Q000378:metabolism* / Q000473:pathology; D017077:Culture Media, Conditioned / Q000737:chemistry; D004247:DNA / Q000032:analysis; D018450:Disease Progression; D010450:Endopeptidases / Q000378:metabolism; D005260:Female; D005342:Fibrinolysis; D005786:Gene Expression Regulation; D006801:Humans; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D010960:Plasminogen Activators / Q000032:analysis / Q000096:biosynthesis* / Q000235:genetics; D012720:Severity of Illness Index
chemical_list: D017077:Culture Media, Conditioned; D017395:Plasminogen Activator Inhibitor 1; D004247:DNA; D010450:Endopeptidases; D010960:Plasminogen Activators