The Role of ADAMTS1 and Versican in Human Myocardial Infarction: A Postmortem Study

Objective: To determine the role of a disintegrin and metalloproteinase with thrombospondin type 1 motif (ADAMTS1) and fragmented versican in the myocardial infarction (MI) process in humans and to evaluate the diagnostic efficacy of ADAMTS1 for postmortem diagnosis of MI. Methods: Thirty autopsied individuals were allocated into 2 groups, namely, a study group of individuals who died of myocardial infarction (n = 20), and a control group who died of trauma (n = 10). We performed standard immunohistochemical staining on myocardial tissue specimens, studying anti-ADAMTS1, anti-versican, and anti-versican C terminal peptide sequence (DPEAAE) fragments. Results: Strong, diffuse staining was observed throughout myocardial tissue for ADAMTS1 in the 2 groups. However, in the study group, we observed no expression for ADAMTS1 around fibrotic areas but detected slight staining in coagulative and necrotic zones. Conclusion: Similar localizations of ADAMTS and fragmented versican in human heart tissue indicate that versican presumably is cleaved by ADAMTS1. Hence, ADAMTS1 can be regarded as a new marker for postmortem differential diagnosis of MI. * Abbreviations : WHO : World Health Organization AMI : acute myocardial infarction MI : myocardial infarction H&E : hematoxylin and eosin FABP : fatty acid-binding protein ECM : extracellular matrix LV : left ventricular MMPs : matrix metalloproteinases ADAMTS1 : a disintegrin and metalloproteinase with thrombospondin type 1 motif VEGF : vascular endothelial growth factor mRNA : messenger RNA PBS : phosphate-buffered saline DPEAAE : C terminal peptide sequence having 6 amino acids CK-MB : creatine kinase–muscle/brain isoform LDH : lactate dehydrogenase TNF-α : tumor necrosis factor–α IL-1 : interleukin 1 M : male F : female LAD : left anterior descending artery LCA : left circumflex artery RCA : right coronary artery LV : left ventricle LVPW : left ventricular posterior wall LVFW : left ventricular free wall CN : coagulation necrosis CA : coronary arteries CB : contraction bands +++ : prominent staining throughout the section - : section exhibited no staining + : occasional staining, with most fields showing slightly negative results NA : not applicable NS : nerve sheath NF : nerve fibers ++ : focally abundant staining with most fields showing positive staining