Drug Targeting of Plasminogen Activator Inhibitor-1 Inhibits Metabolic Dysfunction and Atherosclerosis in a Murine Model of Metabolic Syndrome.

ABSTRACT:

Objective

Enhanced expression of PAI-1 (plasminogen activator inhibitor-1) has been implicated in atherosclerosis formation in humans with obesity and metabolic syndrome. However, little is known about the effects of pharmacological targeting of PAI-1 on atherogenesis. This study examined the effects of pharmacological PAI-1 inhibition on atherosclerosis formation in a murine model of obesity and metabolic syndrome. Approach and Results: LDL receptor-deficient (ldlr^-/-) mice were fed a Western diet high in cholesterol, fat, and sucrose to induce obesity, metabolic dysfunction, and atherosclerosis. Western diet triggered significant upregulation of PAI-1 expression compared with normal diet controls. Addition of a pharmacological PAI-1 inhibitor (either PAI-039 or

SUBMITTER: Khoukaz HB 

PROVIDER: S-EPMC7255962 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature