N(epsilon)-(carboxymethyl)lysine depositions in intramyocardial blood vessels in human and rat acute myocardial infarction: a predictor or reflection of infarction?
OBJECTIVE
Advanced glycation end products (AGEs), such as N(epsilon)-(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.


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.
Baidoshvili
A
A
VU University Medical Center, Department of Pathology, De Boelelaan 1117, 1007 MB Amsterdam, The Netherlands.
Krijnen
P A J
PA
Kupreishvili
K
K
Ciurana
C
C
Bleeker
W
W
Nijmeijer
R
R
Visser
C A
CA
Visser
F C
FC
Meijer
C J L M
CJ
Stooker
W
W
Eijsman
L
L
van Hinsbergh
V W M
VW
Hack
C E
CE
Niessen
H W M
HW
Schalkwijk
C G
CG
D000368:Aged; D000818:Animals; D003331:Coronary Vessels / Q000378:metabolism*; D019040:E-Selectin / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008239:Lysine / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000209:etiology / Q000378:metabolism*; D015425:Myocardial Reperfusion; D009205:Myocarditis / Q000378:metabolism; D018384:Oxidative Stress; D009195:Peroxidase / Q000378:metabolism; D011379:Prognosis; D051381:Rats; D012307:Risk Factors; D013997:Time Factors
D019040:E-Selectin; C048496:N(6)-carboxymethyllysine; D009195:Peroxidase; D008239:Lysine