Fibrosis, not cell size, delineates β-myosin heavy chain reexpression during cardiac hypertrophy and normal aging in vivo

Abstract

Reexpression of the fetally expressed ␤-myosin heavy chain (␤-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 ␤-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 ␤-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 ␤-MHC occurs in discrete subsets of myocytes within the subendocardium rather than uniformly throughout the heart, that ␤-MHC induction is not an obligatory consequence of cellular hypertrophy, and that ␤-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 ␤-MHC gene expression in the normal aging adult and hypertrophic mouse heart is a marker of fibrosis rather than of cellular hypertrophy. genetic reprogramming T he adult myocardium responds to extrinsic forms of stress, such as hypertension, myocardial infarction, and pressure overload, by a hypertrophic growth response (reviewed in ref.

Speckle Tracking Echocardiography Detects Uremic Cardiomyopathy Early and Predicts Cardiovascular Mortality in ESRD

“…Additionally, UC was accompanied by re-expression of the fetally expressed b-myosin heavy chain and increased cardiac expression of brain natriuretic peptide, both of which have been linked to cardiac fibrosis, hypertrophy, and UC. 31,44,45 Our first major finding was that, in rat models, UC led to early changes of myocardial systolic and diastolic deformation detectable by STE, whereas classic echocardiographic parameters of left ventricular function, such as FS or CO, changed only at a later time point, when the rats exhibited greater myocardial fibrosis and hypertrophy. Martin et al recently reported early changes in early diastolic circumferential strain rate assessed by STE in rats with mild renal insufficiency after uninephrectomy.…”

Altered left ventricular performance in aging physically active mice with an ankle sprain injury

“…Therefore, beneficial prescription regarding higher intensity aerobic exercise during the first 40 % of the lifespan will result in the greatest improvements in LV diastolic filling early in life, while higher intensity and longer duration aerobic activity throughout the lifespan results in better diastolic filling parameters near the end of life. Age-related alterations in LV alpha and beta myosin heavy chain (MHC) have been widely investigated in differing species primarily in cross-sectional study designs, with the findings suggesting the amount of beta MHC expression does not change but becomes more indicative of fibrosis while alpha MHC declines in expression relative to the development of heart failure (Gorza et al 1984;Miyata et al 2000;Pandya et al 2006;Reiser et al 2001;Samuel et al 1983). Interestingly, we did not observe any differences in either left ventricular alpha or beta MHC content between a group of highly active mice (SHAM), low active but injured mice (ATFL/ CFL), or sedentary mice (SHAMSED), suggesting similar end of life LV MHC content regardless of lifelong intervention.…”

American Thyroid Association Guide to Investigating Thyroid Hormone Economy and Action in Rodent and Cell Models

“…However, recent studies have shown an unexpected heterogeneity of regulated expression of Myh7 (569,570), and this needs to be taken into account when assessing effects of T 3 .…”