Circulating Prolidase Activity in Patients with Myocardial Infarction

Abstract

BackgroundCollagen is a major determinant of atherosclerotic plaque stability. Thus, identification of differences in enzymes that regulate collagen integrity could be useful for predicting susceptibility to atherothrombosis or for diagnosing plaque rupture. In this study, we sought to determine whether prolidase, the rate-limiting enzyme of collagen turnover, differs in human subjects with acute myocardial infarction (MI) versus those with stable coronary artery disease (CAD).MethodsWe measured serum prolidase activity in 15 patients with stable CAD and 49 patients with acute MI, of which a subset had clearly defined thrombotic MI (n = 22) or non-thrombotic MI (n = 12). Prolidase activity was compared across study time points (at cardiac catheterization, T0; 6 h after presentation, T6; and at a quiescent follow-up, Tf/u) in acute MI and stable CAD subjects. We performed subgroup analyses to evaluate prolidase activity in subjects presenting with acute thrombotic versus non-thrombotic MI.ResultsAlthough prolidase activity was lower at T0 and T6 versus the quiescent phase in acute MI and stable CAD subjects (p < 0.0001), it was not significantly different between acute MI and stable CAD subjects at any time point (T0, T6, and Tf/u) or between thrombotic and non-thrombotic MI groups. Preliminary data from stratified analyses of a small number of diabetic subjects (n = 8) suggested lower prolidase activity in diabetic acute MI subjects compared with non-diabetic acute MI subjects (p = 0.02).ConclusionCirculating prolidase is not significantly different between patients with acute MI and stable CAD or between patients with thrombotic and non-thrombotic MI. Further studies are required to determine if diabetes significantly affects prolidase activity and how this might relate to the risk of MI.

Serum Pirolidase Activity in Cardiovascular Disease

“…In a study comparing patients with acute MI and stable CAD, SPA levels were lower in patients with acute MI (9). This finding suggests that low SPA levels during acute MI indicate severe stress rather than plaque rupture.…”

“…Angiotensin convertase inhibitor (ACE), such as enalapril, has also been shown to affect prolidase activity by affecting the collagen cycle, like antiplatelet agents (11). Patients with acute coronary syndrome (ACS) undergoing percutaneous transluminal coronary angioplasty (PTCA) have lower levels of prolidase activity due to routine acetylsalicylic acid and anticoagulant treatment (9). SPA has been shown independently related to left ventricular diastolic dysfunction, hypertension, coronary artery aneurysm, aortic dilatation, and coronary slow flow (12).…”

Current Understanding of the Emerging Role of Prolidase in Cellular Metabolism

“…The clinical significance of prolidase is reflected in various cancers as well as pathological conditions associated with collagen turnover [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. For instance, increased prolidase activity has been observed in melanoma [ 21 ], breast cancer [ 22 ], lung cancer [ 23 ], ovary cancer [ 24 ], and endometrial cancer [ 25 ].…”

“…To date, no effective PD treatment has been developed [ 3 ]. Moreover, there are reports indicating the clinical relevance of prolidase in collagen metabolism malfunctions [ 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ], metabolic [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ], and oncological disorders [ 21 , 22 , 23 , 24 , 25 ]. In addition to its catalytic activity, prolidase regulates numerous biological processes.…”