Sobel, Burton E.;
Woodcock-Mitchell, Janet;
Schneider, David J.;
Holt, Robert E.;
Marutsuka, Kousuke;
Gold, Herman
Increased Plasminogen Activator Inhibitor Type 1 in Coronary Artery Atherectomy Specimens From Type 2 Diabetic Compared With Nondiabetic Patients : A Potential Factor Predisposing to Thrombosis and Its Persistence
: A Potential Factor Predisposing to Thrombosis and Its Persistence
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Medientyp:
E-Artikel
Titel:
Increased Plasminogen Activator Inhibitor Type 1 in Coronary Artery Atherectomy Specimens From Type 2 Diabetic Compared With Nondiabetic Patients : A Potential Factor Predisposing to Thrombosis and Its Persistence
:
A Potential Factor Predisposing to Thrombosis and Its Persistence
Beteiligte:
Sobel, Burton E.;
Woodcock-Mitchell, Janet;
Schneider, David J.;
Holt, Robert E.;
Marutsuka, Kousuke;
Gold, Herman
Beschreibung:
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<jats:italic>Background</jats:italic>
—Inhibition of fibrinolysis attributable to elevated concentrations of plasminogen activator inhibitor type 1 (PAI-1) in blood is associated with insulin resistance, hyperinsulinemia, and type 2 diabetes mellitus. Because we have shown that insulin can stimulate PAI-1 synthesis in vivo and because accelerated vascular disease is common in such patients as well, we hypothesized that increased PAI-1, potentially predisposing to thrombosis, acute occlusion, and accelerating atherosclerosis because of thrombus-associated mitogens, would be present in excess in atheroma from type 2 diabetic subjects.
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<jats:p>
<jats:italic>Methods and Results</jats:italic>
—Samples acquired by directional coronary atherectomy from 25 patients with type 2 diabetes and 18 patients without diabetes were characterized qualitatively histologically for cellularity and by immunohistochemistry visually and qualitatively and by quantitative image analysis for assessment of urokinase-type plasminogen activator (u-PA) and PAI-1. Patients with and without diabetes were similar with respect to demographic features and the distribution and severity of coronary artery disease. Substantially more PAI-1 and substantially less u-PA were present in the atherectomy samples from subjects with diabetes.
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<jats:p>
<jats:italic>Conclusions</jats:italic>
—The disproportionate elevation of PAI-1 compared with u-PA observed in atheromatous material extracted from vessels of diabetic subjects is consistent with increased gene expression of PAI-1 in vessels as well as the known increase of PAI-1 in blood, presumably reflecting increased synthesis. The increased PAI-1 detected in the atheroma may contribute in vivo to accelerated or persistent thrombosis underlying acute occlusion and to vasculopathy exacerbated by clot-associated mitogens in the vessel wall. Because the changes were observed to be associated with insulin resistance and type 2 diabetes mellitus, they may be modifiable by reduction of insulin resistance with insulin sensitizers and stringent control of hyperglycemia.
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