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

被引:213
作者
Sobel, BE
Woodcock-Mitchell, J
Schneider, DJ
Holt, RE
Marutsuka, K
Gold, H
机构
[1] Univ Vermont, Coll Med, Dept Med, Burlington, VT USA
[2] Massachusetts Gen Hosp, Boston, MA 02114 USA
关键词
diabetes mellitus; coronary disease; fibrinolysis; insulin; thrombosis;
D O I
10.1161/01.CIR.97.22.2213
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background-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. Methods and Results-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. Conclusions-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.
引用
收藏
页码:2213 / 2221
页数:9
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