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Advanced glycation end product accumulation in the cardiomyocytes of heart failure patients with and without diabetes

Jerzy Nożyński, Michał Zakliczyński, Dominika Konecka-Mrowka, Teresa Zielinska, Helena Zakliczynska, Barbara Nikiel, Joanna Mlynarczyk-Liszka, Andrzej Mrowka, Ewa Zembala-Nozynska, Marta Pijet, Kinga Rdzanowska, Dariusz Lange, Roman Przybylski, Marian Zembala

Ann Transplant 2012; 17(2): 53-61

DOI: 10.12659/AOT.883223


Background:    Non-enzymatic coupling of protein and lipid cellular structures with glucose leading to the formation of advanced glycation end products (AGE) plays a role in aging and the development of diabetic complications, but its contribution to myocardial pathology is unclear. We aimed to assess the role of heart failure on AGE formation in patients with or without diabetes mellitus type 2 (DM2).
    Material/Methods:    Heart tissue specimens from 136 patients undergoing transplantation were grouped as follows: 14 cases of ischemic cardiomyopathy (ICM) and DM2, 8 cases of dilated cardiomyopathy (DCM) and DM2, 67 cases of ICM without DM2, and 47 cases of DCM without DM2. Fourteen heart samples were from the autopsies of patients with DM2 without heart disease, and 20 heart samples were from organ donors in whom the heart was wasted. AGE deposits were localized immunohistochemically counted using a semiquantitative scale and characterized by their staining pattern.
    Results:    Positive staining was present in all samples from both cardiomyopathy groups with DM2, in 71% of healthy hearts from the DM2 subjects, in 51% of ICM non-diabetic hearts, and in 38% of DCM non-diabetic hearts, and in only 15% of the organ donors. Mixed-diffuse and granular AGE patterns were characteristic for DM2, while a diffuse pattern was more frequently observed in heart failure patients without diabetes. The semiquantitative results supported increased AGE accumulation in patients with DM2 and/or cardiomyopathy.
    Conclusions:    The amount of AGE in cardiomyocytes increases significantly in both diabetes and heart failure, with a staining pattern typical for each condition.

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