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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2006;26:2497.)
© 2006 American Heart Association, Inc.

Vascular Biology

N-(Carboxymethyl)lysine Depositions in Intramyocardial Blood Vessels in Human and Rat Acute Myocardial Infarction

A Predictor or Reflection of Infarction?

A. Baidoshvili; P.A.J. Krijnen; K. Kupreishvili; C. Ciurana; W. Bleeker; R. Nijmeijer; C.A. Visser; F.C. Visser; C.J.L.M. Meijer; W. Stooker; L. Eijsman; V.W.M. van Hinsbergh; C.E. Hack; H.W.M. Niessen; C.G. Schalkwijk

From the Departments of Pathology (A.B., P.A.J.K., K.K., R.N., C.J.L.M.M., H.W.M.N.), Cardiology (R.N., C.A.V., F.C.V.), Physiology (V.W.M.v.H.), and Clinical Chemistry (C.E.H., C.G.S.), VU University Medical Center, Amsterdam; ICaR-VU (A.B., P.A.J.K., K.K., R.N., C.A.V., F.C.V., W.S., V.W.M.v.H., C.E.H., H.W.M.N., C.G.S.), Amsterdam; Department of Immunopathology (C.C., W.B., C.E.H.), Sanquin Research at CLB, Amsterdam; Genmab (W.B.), Utrecht; Department of Cardiac Surgery (W.S., L.E.), OLVG, Amsterdam; and Department of Internal Medicine (C.G.S.), University of Maastricht, the Netherlands.

Correspondence to H.W.M. Niessen, VU University Medical Center, Department of Pathology, De Boelelaan 1117, 1007 MB Amsterdam, the Netherlands. E-mail jwm.niessen{at}vumc.nl

Objective— Advanced glycation end products (AGEs), such as N-(carboxymethyl)lysine (CML), are implicated in vascular disease. We previously reported increased CML accumulation in small intramyocardial blood vessels in diabetes patients. Diabetes patients have an increased risk for acute myocardial infarction (AMI). Here, we examined a putative relationship between CML and AMI.

Methods and Results— Heart tissue was stained for CML, myeloperoxidase, and E-selectin in AMI patients (n=26), myocarditis patients (n=17), and control patients (n=15). In AMI patients, CML depositions were 3-fold increased compared with controls in the small intramyocardial blood vessels and predominantly colocalized with activated endothelium (E-selectin–positive) both in infarction and noninfarction areas. A trend of increased CML positivity of the intima of epicardial coronary arteries did not reach significance in AMI patients. In the rat heart AMI model, CML depositions were undetectable after 24 hours of reperfusion, but became clearly visible after 5 days of reperfusion. In line with an inflammatory contribution, human myocarditis was also accompanied by accumulation of CML on the endothelium of intramyocardial blood vessels.

Conclusions— CML, present predominantly on activated endothelium in small intramyocardial blood vessels in patients with AMI, might reflect an increased risk for AMI rather than being a result of AMI.

We examined a putative relationship between CML and AMI. CML depositions were significantly increased on activated endothelium of intramyocardial blood vessels after AMI and in myocarditis. In vitro and in the rat CML was upregulated by inflammation, not by ischemia. In AMI patients, CML is probably present in advance of the AMI.

Key Words: acute myocardial infarction • AGEs • CML • endothelium • myocarditis • vascular disease

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