Abstract
Experimental studies showed that plasminogen activator inhibitor-1 (PAI-1) is abundantly expressed in the infarcted myocardium and that the increased PAI-1 expression causes an impairment of fibrinolysis in the coronary vascular beds and left ventricular (LV) adverse remodeling after acute myocardial infarction (AMI). However, little is known in humans. Thus, this study examined whether PAI-1 produced in the infarcted lesion may contribute to coronary endothelial dysfunction and LV dysfunction in patients with AMI. Methods: Plasma levels of PAI-1 activity and tissue-plasminogen activator (tPA) protein were measured by ELISA in plasma obtained from aortic root (AO), anterior interventricular vein (AIV), and peripheral vein (PV) in 41 patients with a first AMI due to occlusion of a proximal segment of the LAD at 6 months (M) after MI. Coronary blood flow responses in the LAD to intracoronary infusion of acetylcholine (ACh, 50 μg/min) were measured by an intracoronary flow wire technique 6M after MI. Left ventriculography was repeated twice, 2 weeks (2W) and 6M after MI. Results: The trans-myocardial gradient of PAI-1 from AO to AIV (0.14 ± 0.15 ng/mL), reflecting a production/release of PAI-1 from the infarcted lesion, had an inverse correlation with coronary blood flow response to ACh (r = -0.43 , p = 0.02). The trans-myocardial gradient of PAI-1 had an inverse correlation with the % changes in LV regional motion in the LAD territory from 2W to 6M after MI (r = -0.37, p = 0.02). PAI-1 level in the PV and the trans-myocardial gradient of tPA had no significant correlation with the coronary blood flow response to ACh and the LV regional motion. The trans-myocardial gradient in PAI-1 level was lower in patients taking than not taking angiotensin II receptor blocker (ARB) (n = 22, -0.15 ± 0.19 ng/mL vs. n = 19, 0.48 ± 0.21 ng/mL, respectively, p = 0.03). Conclusions: PAI-1 produced in the infarcted myocardium and released into the coronary circulation was associated with endothelial dysfunction in resistance vessels of the infarct-related coronary arteries and progressive dysfunction of the infarcted region of LV in AMI survivors. ARB might inhibit PAI-1 production in the infarcted myocardium in the chronic phase of MI, which may represent an additional benefit of ARB therapy.
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