Contractile and cytoskeletal content, structure, and mRNA levels with tachycardia-induced cardiomyopathy.
Chronic supraventricular tachycardia (SVT)-induced cardiomyopathy is associated with left ventricular (LV) dilatation, increased wall stress, neurohormonal activation, and no change in LV mass. To determine mechanisms for changes in LV geometry and function with SVT cardiomyopathy, LV and myocyte function, contractile protein content and mRNA levels, and cytoskeletal protein structure and mRNA levels were examined in 12 pigs with SVT cardiomyopathy (paced at 240 beats/min for 3 wk) and in 12 controls. With SVT cardiomyopathy, LV fractional shortening fell by 61%, and end-diastolic dimension increased by 42%, with no change in LV mass-to-body weight ratio (3.36 +/- 0.15 vs. 3.14 +/- 0.13 g/kg). Myocyte contractile function was reduced by 33%, myocyte length was increased by 28%, and cross-sectional area was decreased by 19% with SVT cardiomyopathy. Total protein, myosin heavy chain (MHC), and actin appeared unchanged with SVT cardiomyopathy at the LV or myocyte level. Moreover, there was no change in mRNA levels for MHC (0.57 +/- 0.05 vs. 0.59 +/- 0.09 mRNAOD/rRNAOD) or cardiac alpha-actin (0.58 +/- 0.08 vs. 0.58 +/- 0.04 mRNAOD/rRNAOD) with SVT cardiomyopathy. In contrast, mRNA levels for specific cytoskeletal proteins were significantly increased with SVT cardiomyopathy, and immunofluorescent localization of contractile and cytoskeletal proteins in isolated myocytes revealed alterations in cytoskeletal architecture. Thus changes in LV and myocyte geometry with SVT cardiomyopathy were associated with no change in contractile protein content or mRNA at the chamber or myocyte level. Furthermore, increased cytoskeletal protein abundance and mRNA and reorientation of cardiocyte cytoarchitecture may have contributed to the LV and myocyte remodeling with SVT cardiomyopathy.
Eble
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DM
Division of Cardiothoracic Surgery, Medical University of South Carolina, Charleston 29425, USA.
Spinale
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FG
D000199:Actins / Q000378:metabolism; D000818:Animals; D009202:Cardiomyopathies / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D003285:Contractile Proteins / Q000096:biosynthesis / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004452:Echocardiography; D015870:Gene Expression; D006339:Heart Rate; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism*; D012016:Reference Values; D013552:Swine; D013610:Tachycardia / Q000503:physiopathology*; D016277:Ventricular Function, Left
D000199:Actins; D003285:Contractile Proteins; D003598:Cytoskeletal Proteins; D012333:RNA, Messenger; D004247:DNA