Fibrosis, not cell size, delineates beta-myosin heavy chain reexpression during cardiac hypertrophy and normal aging in vivo.
Reexpression of the fetally expressed beta-myosin heavy chain (beta-MHC) gene is a well documented marker of pathological cardiac hypertrophy and normal aging in many experimental models. To gain insights into factors affecting this reexpression of beta-MHC within the complex anatomical structure of the heart, we investigated the spatial pattern of its expression at the level of single cells during aging and hypertrophy. We generated mice that express yellow fluorescent protein fused to the N terminus of the beta-MHC and examined its expression pattern during normal aging and in mice with hypertrophy induced by constitutive expression of a renin transgene. The localization of fibrosis within the hearts also was determined by using a fluorescent lectin. The results show that reexpression of beta-MHC occurs in discrete subsets of myocytes within the subendocardium rather than uniformly throughout the heart, that beta-MHC induction is not an obligatory consequence of cellular hypertrophy, and that beta-MHC-expressing cells in the normal aging heart and the hypertrophic heart are distributed predominantly in clusters within and surrounding foci of fibrosis. We conclude that beta-MHC gene expression in the normal aging adult and hypertrophic mouse heart is a marker of fibrosis rather than of cellular hypertrophy.
Pandya
Kumar
K
Department of Pathology and Laboratory Medicine, University of North Carolina, Chapel Hill, NC 27599, USA.
Kim
Hyung-Suk
HS
Smithies
Oliver
O
D000375:Aging / Q000235:genetics* / Q000473:pathology*; D000818:Animals; D000831:Animals, Newborn; D001426:Bacterial Proteins / Q000235:genetics; D006332:Cardiomegaly / Q000235:genetics* / Q000473:pathology*; D049108:Cell Enlargement; D048429:Cell Size; D005260:Female; D005355:Fibrosis; D018507:Gene Expression Regulation, Developmental; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000235:genetics*; D024723:Ventricular Myosins / Q000235:genetics*
D001426:Bacterial Proteins; D008164:Luminescent Proteins; C054562:yellow fluorescent protein, Bacteria; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains