title: An altered pattern of myocardial histopathological and molecular changes underlies the different characteristics of type-1 and type-2 diabetic cardiac dysfunction.
abstract: 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. 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. Marked systolic dysfunction in type-1 DM was associated with severe nitrooxidative 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, was elevated in type-1, while it remained unaltered or only slightly increased in type-2 DM. Expression of the profibrotic TGF-β 1 was upregulated in type-1 and showed a decrease in type-2 DM. We compared type-1 and type-2 diabetic cardiomyopathy in standard rat models and described an altered pattern of key pathophysiological features in the diabetic heart and corresponding functional consequences.
authors: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, 69120 Heidelberg, Germany ; Heart and Vascular Center, Semmelweis University, Városmajor u. 68, 1122 Budapest, Hungary.
authors: Tamás
authors: T
authors: Radovits
authors: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, 69120 Heidelberg, Germany.
authors: Sevil
authors: S
authors: Korkmaz
authors: Heart and Vascular Center, Semmelweis University, Városmajor u. 68, 1122 Budapest, Hungary.
authors: Csaba
authors: C
authors: Mátyás
authors: Heart and Vascular Center, Semmelweis University, Városmajor u. 68, 1122 Budapest, Hungary.
authors: Attila
authors: A
authors: Oláh
authors: Heart and Vascular Center, Semmelweis University, Városmajor u. 68, 1122 Budapest, Hungary.
authors: Balázs Tamás
authors: 0000-0001-7202-8107
authors: BT
authors: Németh
authors: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, 69120 Heidelberg, Germany ; Heart and Vascular Center, Semmelweis University, Városmajor u. 68, 1122 Budapest, Hungary.
authors: Szabolcs
authors: S
authors: Páli
authors: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, 69120 Heidelberg, Germany.
authors: Kristóf
authors: 0000-0003-3392-6021
authors: K
authors: Hirschberg
authors: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, 69120 Heidelberg, Germany.
authors: Alina
authors: A
authors: Zubarevich
authors: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, 69120 Heidelberg, Germany.
authors: Patricia Neh
authors: PN
authors: Gwanmesia
authors: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, 69120 Heidelberg, Germany.
authors: Shiliang
authors: S
authors: Li
authors: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, 69120 Heidelberg, Germany.
authors: Sivakkanan
authors: S
authors: Loganathan
authors: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, 69120 Heidelberg, Germany ; Heart and Vascular Center, Semmelweis University, Városmajor u. 68, 1122 Budapest, Hungary.
authors: Enikő
authors: E
authors: Barnucz
authors: Heart and Vascular Center, Semmelweis University, Városmajor u. 68, 1122 Budapest, Hungary.
authors: Béla
authors: B
authors: Merkely
authors: Department of Cardiac Surgery, University of Heidelberg, INF 326 OG 2, 69120 Heidelberg, Germany.
authors: Gábor
authors: G
authors: Szabó
mesh_terms: D000818:Animals; D017209:Apoptosis; D048909:Diabetes Complications / Q000503:physiopathology; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology; D003922:Diabetes Mellitus, Type 1 / Q000503:physiopathology*; D003924:Diabetes Mellitus, Type 2 / Q000503:physiopathology*; D005355:Fibrosis; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology; D006331:Heart Diseases / Q000150:complications*; D006439:Hemodynamics; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D009206:Myocardium / Q000473:pathology*; D018384:Oxidative Stress; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011924:Rats, Zucker; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000737:chemistry; D016277:Ventricular Function, Left
chemical_list: D012333:RNA, Messenger; D053773:Transforming Growth Factor beta1; C002744:3-nitrotyrosine; D014443:Tyrosine
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