Advanced glycation end products in the development of ischemic and dilated cardiomyopathy in patients with diabetes mellitus type 2.
BACKGROUND
Hyperglycemia intensifies nonenzymatic glucose coupling to tissues, resulting in myocardial stiffness and formation of advanced glycation end products (AGE). The aim of this study was to assess seeking AGE in the myocardium from patients with type 2 diabetes (DM2) subjected to orthotopic heart transplantation (OHT), seeking to establish whether AGE play a role in the development of cardiomyopathies leading to OHT.


METHODS
The 2 studied groups consisted of 11 hearts explanted from patients with ischemic cardiomyopathy+DM2 (ICM+DM2, 55 +/- 6.5 years) and 8 from dilated cardiomyopathy+DM2 (DCM+DM2, 49.6 +/- 4.5 years). Comparative subgroups were composed of nondiabetic explanted hearts, 41 with ICM (52.8 +/- 5.8 years) and 41 with DCM (52.7 +/- 4.2 years). All patients were males.


METHODS
We examined immunohistochemical localization of AGE using a semiquantitative scale of reaction intensity in cardiomyocytes, fibroblasts, capillaries, arterioles, and arteries. Additionally, we calculated the scores for cardiocytes (AGE(Cardiocyte)) and all left ventricular components (AGE(LV)).


RESULTS
The cytoplasmic AGE deposits in cardiomyocytes were predominantly diffuse-granular in DM2 groups, whereas nondiabetic groups showed a lack of a reaction or a diffuse pattern. There were no differences in the reaction intensity between the 2 studied groups, or 2 comparative groups. All myocardial constituents showed higher AGE intensity in DM2 than nondiabetic groups. Only in the ICM+DM2 group did the DM2 duration correlate with AGE staining in selected myocardial layers and with AGE(Cardiocyte) and AGE(LV).


CONCLUSIONS
The presence of AGE in the hearts of patients requiring transplantation was related to the duration of DM2. The deposition of AGE in left ventricular myocardium was enhanced by DM2 particularly in patients with ICM.
Nozyński
J
J
Department of Cardiac Surgery & Transplantation, Silesian Center for Heart Disease, Zabrze, Poland.
Zakliczyński
M
M
Konecka-Mrówka
D
D
Nikiel
B
B
Mlynarczyk-Liszka
J
J
Zembala-Nozyńska
E
E
Lange
D
D
Maruszewski
M
M
Zembala
M
M
D000328:Adult; D001160:Arterioles / Q000503:physiopathology; D002196:Capillaries / Q000503:physiopathology; D002311:Cardiomyopathy, Dilated / Q000453:epidemiology* / Q000601:surgery; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D003925:Diabetic Angiopathies / Q000453:epidemiology / Q000601:surgery*; D006442:Glycated Hemoglobin / Q000378:metabolism; D017127:Glycation End Products, Advanced / Q000502:physiology*; D016027:Heart Transplantation / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000453:epidemiology* / Q000601:surgery; D032383:Myocytes, Cardiac / Q000502:physiology
D006442:Glycated Hemoglobin; D017127:Glycation End Products, Advanced