Cardiomyocyte-specific desmin rescue of desmin null cardiomyopathy excludes vascular involvement.
Mice deficient in desmin, the muscle-specific member of the intermediate filament gene family, display defects in all muscle types and particularly in the myocardium. Desmin null hearts develop cardiomyocyte hypertrophy and dilated cardiomyopathy (DCM) characterized by extensive myocyte cell death, calcific fibrosis and multiple ultrastructural defects. Several lines of evidence suggest impaired vascular function in desmin null animals. To determine whether altered capillary function or an intrinsic cardiomyocyte defect is responsible for desmin null DCM, transgenic mice were generated to rescue desmin expression specifically to cardiomyocytes. Desmin rescue mice display a wild-type cardiac phenotype with no fibrosis or calcification in the myocardium and normalization of coronary flow. Cardiomyocyte ultrastructure is also restored to normal. Markers of hypertrophy upregulated in desmin null hearts return to wild-type levels in desmin rescue mice. Working hearts were perfused to assess coronary flow and cardiac power. Restoration of a wild-type cardiac phenotype in a desmin null background by expression of desmin specifically within cardiomyocyte indicates that defects in the desmin null heart are due to an intrinsic cardiomyocytes defect rather than compromised coronary circulation.
Weisleder
Noah
N
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza Texas Medical Center, Houston, TX 77030, USA.
Soumaka
Elisavet
E
Abbasi
Shahrzad
S
Taegtmeyer
Heinrich
H
Capetanaki
Yassemi
Y
D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D009202:Cardiomyopathies / Q000235:genetics / Q000378:metabolism* / Q000473:pathology* / Q000503:physiopathology; D003326:Coronary Circulation / Q000502:physiology; D003893:Desmin / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D008854:Microscopy, Electron; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics; D019076:Transgenes / Q000235:genetics; D024723:Ventricular Myosins / Q000235:genetics
D003893:Desmin; D024723:Ventricular Myosins