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

Abstract

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 (nϭ26), myocarditis patients (nϭ17), and control patients (nϭ15). 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.

Molecular determinants of heart failure with normal left ventricular ejection fraction

“…In addition, AGE deposition can indirectly augment diastolic LV stiffness through enhanced collagen formation and reduced nitric oxide bioavailability. Indeed, enhanced collagen formation in the presence of AGEs was confirmed in our recent study [40], and low myocardial nitric oxide bioavailability was previously demonstrated in HFREF patients [4,5]. Postmyocarditis patients with HFREF frequently show signs of persistent myocardial microvascular inflammation [38].…”

“…Postmyocarditis patients with HFREF frequently show signs of persistent myocardial microvascular inflammation [38]. This inflammation may facilitate AGE deposition [4] and may explain the preferential AGE deposition in small intramyocardial vessels of diabetic patients with HFREF. The clinical importance of endothelial AGE deposition was recently confirmed in hypertensive patients who showed im- Pharmacological Reports, 2009, 61, 139-145 proved endothelial function with a cross-link breaker [43].…”

Plasma advanced glycation end-products and skin autofluorescence are increased in COPD

“…The cardiovascular complications in diabetes are postulated to be due to the high levels of AGEs in the circulation [40]. In addition, CML has been found on the inner walls of arteries in patients suffering from an acute myocardial infarction in the absence of diabetes [41]. Importantly, in the present study diabetics were excluded and other comorbidities were not frequent enough to investigate their contribution to the increased AGE levels in COPD.…”

Diabetes Mellitus Worsens Diastolic Left Ventricular Dysfunction in Aortic Stenosis Through Altered Myocardial Structure and Cardiomyocyte Stiffness

“…Development of the anti-CML monoclonal antibody used and the immunohistochemical staining technique have previously been described. 27,28 An immunohistochemical AGE score per square millimeter is reported and was derived as follows: Each positively stained vessel was given an intensity grade (1ϭweak staining, 2ϭmoderate staining, 3ϭintense staining), and the sum of all positively stained vessels multiplied by their intensity grade was subsequently divided by the slide area to yield an AGE score per square millimeter.…”