Different role of advanced glycation end products in pathology of transplanted heart in patients with or without diabetes mellitus type 2.
BACKGROUND
Aim of the study was to localize advanced glycation end products (AGEs) in late endomyocardial biopsies (EMBs) of orthotopic heart transplant (OHT) recipients with and without diabetes mellitus (DM) to correlate their presence with acute rejection episodes (ARE) and cardiac allograft vasculopathy (CAV).


METHODS
Elective EMBs were performed at 3 years post-OHT in 64 subjects, with DM (59 M/5 F), of overall mean age of 49 +/- 8 years and 24 patients, without DM (21 M/3 F), of overall mean age of 42 +/- 10y. Localization of myocardial AGEs in paraffin sections was assessed immunochemically using mouse monoclonal anti-AGE antibodies (clone 6d12) on cardiomyocytes, stromal cells, connective tissue elements and capillaries.


RESULTS
The occurrence of AGEs was similar in DM versus non-DM subjects: namely, cardiocytes 73% versus 63%, stroma 33% versus 33%, connective tissue 13% versus 9%, and capillaries 31% versus 33%, respectively. Only in the DM group. The acute rejection episodes and mean EMB score significantly correlated with AGE presence in cardiomyocytes (r = 0.29/0.3; P = .02/.02; Spearman). There was no relation between AGE occurrence and CAV diagnosis among DM subjects, while the time free from angiographically confirmed CAV or a CAV-related event was significantly shorter among non-DM recipients without AGEs in capillaries and/or cardiocytes (P = .014/.017/.014/.03, respectively; log-rank).


CONCLUSIONS
AGE occurrence in OHT recipients with DM was related to ARE, but not to CAV; in contrast, among non-DM patients it was not correlated with ARE, but their absence predicted CAV.
Dept. of Cardiac Surgery & Transplantation, Silesian Center for Heart Diseases, ul. Szpitalna 2, 41-800 Zabrze, Poland. m.zakliczynski@sccs.pl
M
M
Zakliczynski
J
J
Nozynski
D
D
Konecka-Mrowka
L
L
Pyka
D
D
Trybunia
B
B
Nikiel
J
J
Mlynarczyk-Liszka
D
D
Lange
M
M
Zembala
D000328:Adult; D003924:Diabetes Mellitus, Type 2 / Q000150:complications* / Q000473:pathology*; D003925:Diabetic Angiopathies / Q000473:pathology / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D017127:Glycation End Products, Advanced / Q000032:analysis / Q000378:metabolism*; D016027:Heart Transplantation / Q000473:pathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000473:pathology; D010865:Pilot Projects; D012189:Retrospective Studies; D014019:Tissue Donors / Q000706:statistics & numerical data
D017127:Glycation End Products, Advanced