PAPP-A: A possible pathogenic link to the instability of atherosclerotic plaque

Abstract

The rupture of coronary atherosclerotic plaque and subsequent thrombus formation are major events underlying acute coronary syndromes (ACS). Pregnancy associated plasma protein A (PAPP-A) is a member of the metzincin superfamily of metalloproteinases originally identified in the serum of pregnant women. Recent studies indicate that ACS is associated with elevated serum concentrations of PAPP-A. PAPP-A level is not only a marker of plaque instability favoring the progression to myocardial infarction, but is indicative of a poor prognosis even after the occurrence of an acute ischemic event caused by plaque instability. Why PAPP-A expression in unstable plaques is high is a puzzling problem. We hypothesized that PAPP-A is a possible cause of the instability of atherosclerotic plaque which plays a role in ACS. Studies found that PAPP-A was abundantly expressed in both eroded and ruptured plaques, but was only minimally expressed in stable plaques. Other studies have also demonstrated that patients with hyperechoic or isoechoic carotid plaques exhibit significantly higher PAPP-A levels than those with hypoechoic early carotid lesions. If the hypothesis is confirmed, administration of PAPP-A monoclonal antibodies may be used to eliminate the pathogen. It will be a new target point to treat ACS.