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Ultrastructural changes associated with myocardial apoptosis, in failing rat hearts induced by volume overload

Item Type:Article
Title:Ultrastructural changes associated with myocardial apoptosis, in failing rat hearts induced by volume overload
Creators Name:Treskatsch, S. and Shakibaei, M. and Feldheiser, A. and Shaqura, M. and Dehe, L. and Roepke, T.K. and Spies, C. and Schaefer, M. and Mousa, S.A.
Abstract:BACKGROUND: Myocardial apoptosis has been discussed to play a pivotal role in the development and progression of congestive heart failure (CHF). However, recently there is doubt on the evidence of myocardial apoptosis in heart failure as information on ultrastructural changes by electron microscopy is still scarce. This project therefore aimed to detect direct morphological evidence of myocardial apoptosis in an experimental heart failure model. METHOD: Following IRB approval, an aortocaval fistula (ACF) was induced in male Wistar rats using a 16G needle. 28+/-2days following ACF rats were examined by hemodynamic measurements, Western blot, immunofluorescence confocal and electron microscopic analysis. RESULTS: Within 28+/-2days of ACF heart (3.8+/-0.1 vs. 6.6+/-0.3mg/g) and lung (3.7+/-0.2 vs. 6.9+/-0.5mg/g) weight indices significantly increased in the ACF group accompanied by a restriction in systolic (LVEF: 72+/-2 vs. 39+/-3%) and diastolic (dP/dtmin.: -10,435+/-942 vs. -5982+/-745mmHg/s) function (p<0.01). Activated caspase-3 was significantly increased in failing hearts concomitant with mitochondrial leakage of cytochrome c into the cytosol. Finally, electron microscopy of the left ventricle (LV) of ACF rats revealed pronounced ultrastructural changes in >70% of examined cardiomyocytes, such as nuclear chromatin condensation, myofibril loss and disarray, contour irregularities and amorphous dense bodies, mitochondriosis and damaged cell-cell-contacts between cardiomyocytes. CONCLUSIONS: Volume overload induced heart failure is associated with activation of the mitochondrial apoptotic pathway. In addition, electron microscopy of the LV revealed direct ultrastructural evidence of extended myocardial apoptosis in ACF rats.
Keywords:Volume Overload, Heart Failure, Apoptosis, Caspase-3, Cytochrome c, Electron Microscopy, Animals, Rats
Source:International Journal of Cardiology
Page Range:327-332
Date:15 October 2015
Official Publication:https://doi.org/10.1016/j.ijcard.2015.06.067
PubMed:View item in PubMed

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