An altered pattern of myocardial histopathological and molecular changes underlies the different characteristics of type-1 and type-2 diabetic cardiac dysfunction
█ Original article
Mátyás Csaba1*, Sayour Alex Ali1*, Korkmaz-Icöz Sevil2, Oláh Attila1, Németh Balázs Tamás1, Páli Szabolcs1, 2, Hirschberg Kristóf2, Zubarevich Alina2, Gwanmesia Patricia Neh2, Li Shiliang2, Loganathan Sivakkanan2, Barnucz Enikő1, 2, Merkely Béla1, Szabó Gábor2, Radovits Tamás1, 2
1Semmelweis Egyetem, Városmajori Szív- és Érgyógyászati Klinika, Kísérleti Kutató Laboratórium, Budapest
2Ruprecht-Karls Egyetem, Szívsebészeti Klinika, Kísérleti Kutató Laboratórium, Heidelberg, Németország
*A szerzők a munkához egyenlő mértékben járultak hozzá
Aims: Increasing evidence suggests that both types of diabetes mellitus (DM) lead to cardiac structural and functional changes. In this study we investigated and compared functional characteristics and underlying subcellular pathological features in rat models of type-1 and type-2 diabetic cardiomyopathy.
Methods: Type-1 DM was induced by streptozotocin. For type-2 DM, Zucker-diabetic fatty (ZDF) rats were used. Left ventricular pressure-volume analysis was performed to assess cardiac function. Myocardial nitrotyrosine immunohistochemistry, TUNEL-assay, hematoxylin-eosin and Masson’s trichrome staining were performed. mRNA and protein expression were quantified by qRT-PCR and Western blot.
Results: Marked systolic dysfunction in type-1 DM was associated with severe oxidative stress, apoptosis and fibrosis. These pathological features were less pronounced or absent, while cardiomyocyte hypertrophy was comparable in type-2 DM, which was associated with unaltered systolic function and increased diastolic stiffness. mRNA-expression of hypertrophy markers c-fos, c-jun and β-MHC, as well as pro-apoptotic caspase-12 were elevated in type-1, while remained unaltered or only slightly increased in type-2 DM. Expression of the profibrotic TGF-β1 was upregulated in type-1 and showed a decrease in type-2 DM.
Conclusions: We compared type-1 and type-2 diabetic cardiomyopathy in standard rat models, described an altered pattern of key pathophysiological features in the diabetic heart and corresponding functional consequences.