Elevated Plasma Plasminogen Activator Inhibitor Type-1 is an Independent Predictor of Coronary Microvascular Dysfunction in Hypertension

Abstract

Background Elevated plasma plasminogen activator inhibitor-1 (PAI-1) is related to cardiovascular events, but its role in subclinical coronary microvascular dysfunction remains unknown. Thus, in the present study it was investigated whether elevated plasma PAI-1 activity is associated with coronary microvascular dysfunction in hypertensive patients. Methods and ResultsThirty patients with untreated essential hypertension and 10 age-matched healthy controls were studied prospectively. Myocardial blood flow (MBF) was measured by using 15 O-water positron emission tomography. Clinical variables associated with atherosclerosis (low-density lipoprotein-cholesterol, high-density lipoprotein (HDL)-cholesterol, triglyceride, homeostasis model assessment (HOMA-IR), and PAI-1 activity) were assessed to determine their involvement in coronary microvascular dysfunction. Adenosine triphosphate (ATP)-induced hyperemic MBF and coronary flow reserve (CFR) were significantly lower in hypertensive patients than in healthy controls (ATP-induced MBF: 2.77±0.82 vs 3.49±0.71 ml·g -1 ·min -1 ; p<0.02 and CFR: 2.95±1.06 vs 4.25±0.69; p<0.001). By univariate analysis, CFR was positively correlated with HDL-cholesterol (r=0.46, p<0.02), and inversely with HOMA-IR (r=-0.39, p<0.05) and PAI-1 activity (r=-0.61, p<0.001). By multivariate analysis, elevated PAI-1 activity remained a significant independent determinant of diminished CFR. Conclusions Elevated plasma PAI-1 activity was independently associated with coronary microvascular dysfunction, which suggests that plasma PAI-1 activity is an important clue linking hypofibrinolysis to the development of atherosclerosis. (Circ J 2007; 71: 348 -353)

Altered Interaction Between Plasminogen Activator Inhibitor Type 1 Activity and Sympathetic Nerve Activity With Aging

“…In humans, elevation of PAI-1 levels occurs in several thrombotic conditions in atherosclerotic patients and aged subjects. [27][28][29][30][31] These results are consistent with our findings in the present aged subjects, but not in the young subjects. The acute reflex of the SNS during LBNP in the young subjects appeared to decrease PAI-1 activity or change it slightly, which might contribute to the defense mechanism against hypercoagulation in the central hypovolemic state.…”

Hypercoagulability Markers in Patients with Peripheral Arterial Disease: Association to Ankle-brachial Index

“…10 Prothrombin F1þ2 constitutes an important marker in vivo of thrombin generation, with potential value to discriminate individuals at risk of developing thrombosis. 11,12 In the same way, high levels of plasminogen activator inhibitor type 1 (PAI-1) are described in diverse thromboembolic states, as in coronary artery disease (CAD), in MI, [13][14][15] and in PAD. 16 In individuals who had suffered MI, fibrinolytic activity is diminished because of increased PAI-1 activity.…”

PAI-1 in Myocardial Remodeling: Is Pharmacological Suppression by ARB Beneficial?

“…An increase in plasma PAI-1 concentration is associated with recurrent coronary events in the survivors of acute myocardial infarction (AMI). Elevated PAI-1 activity is associated with coronary microvascular dysfunction 1) . Although PAI-1-deficient mice exhibit no apparent abnormalities, Iwaki et al previously reported that PAI-1 deficiency in humans can cause a severe bleeding tendency and impairment of wound healing 2) , suggesting an important role of PAI-1 in thrombosis and hemostasis in humans.…”