© 1997 American Heart Association, Inc.
Articles |
Changes in Arterial Expression of Fibrinolytic System Proteins in Atherogenesis
From the Departments of Medicine, Pathology (D.J.T.) and Surgery (J.C.R., B.J.L.), University of Vermont, Burlington, Vt.
Correspondence to David J. Schneider, MD, Department of Medicine, Cardiovascular Division, E217 Given Building, University of Vermont, Burlington, Vt. E-mail djschnei{at}zoo.uvm.edu
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
.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.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.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.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.
Key Words: atherosclerosis • plasminogen activators • plasminogen activator inhibitor type I • arterial wall
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