Effect of plasminogen activator inhibitor-1 in diabetes mellitus and cardiovascular disease

被引:107
作者
Lyon, CJ [1 ]
Hsueh, WA [1 ]
机构
[1] Univ Calif Los Angeles, Div Endocrinol Diabet & Hypertens, Los Angeles, CA 90095 USA
关键词
D O I
10.1016/j.amjmed.2003.08.014
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Concentrations of plasminogen activator inhibitor-1 (PAI-1) are elevated beginning at the stage of impaired glucose tolerance and continuing through the development of diabetes mellitus and the metabolic syndrome. Evolving evidence of the central role of PAI-1 in mediating fibrosis and thrombosis increasingly supports the theory that it is a significant risk factor for macrovascular complications and cardiovascular disease, particularly in patients with diabetes. Several clinical studies have demonstrated a strong correlation between circulating PAI-1 levels and cardiovascular events and mortality. With the potentially severe effects of elevated PAI-1 levels becoming evident, there is increased interest in developing therapies targeted at reducing PAI-1 expression or circulating concentrations. Thus far, weight loss, inhibitors of the renin-angiotensin system, and insulin sensitization through use of thiazolidinediones (TZDs) appear to be the most promising strategies for managing elevated PAI-1 levels. Of these, TZD therapy is the only one that provides the benefits of both long-term glycemic control and improved cardiovascular risk profile. This article reviews the regulation of PAI-1, its activity in various disease states, and available treatment options. (C) 2003 by Excerpta Medica, Inc.
引用
收藏
页码:62 / 68
页数:7
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