Aims: Fibrosis and myocyte hypertrophy are classical remodeling parameters in heart failure (HF); however, an intriguing possibility is that myocytes undergo intracellular remodeling which decrease compliance, contributing to diastolic dysfunction. The most obvious candidates are cytoskeletal proteins. The cytoskeletal protein desmin reinforces the sarcomeres, enabling force generation. As a contributor to sarcomere performance, desmin may represent a better appraisal of dysfunction than fibrosis or myocyte hypertrophy. Main methods: HF was induced in sheep via coronary microembolization. Echocardiography was performed at baseline, 4-, and 12-months in HF. Desmin, fibrosis, and myocyte hypertrophy from infarcted LV posterior and noninfarcted LV anterior walls were measured using Western blot, immunohistochemistry, and digital image analysis. Multivariate regression analysis was performed, providing structure/function mechanisms. *p < 0.05. Key findings: EF decreased from 55% to 24%*. LV end-diastolic area (LVEDA) increased 123%* at month-12. Fibrosis increased only in posterior LV whereas myocyte hypertrophy increased in both LV posterior and LV anterior regions but only at month-12. Desmin content progressively increased 121%* at month-4 and 182%* at month-12 in both LV posterior and anterior walls. Multivariate linear regression (beta coefficient standardization) demonstrated that desmin was a much better predictor of EF (β = - 0.38*) and LVEDA (β = 0.58*) than fibrosis or myocyte hypertrophy. Significance: Desmin, fibrosis, and myocyte hypertrophy are temporally and spatially heterogeneous in HF. Desmin content more accurately correlated with remodeling than fibrosis or myocyte hypertrophy, suggesting that intra-myocyte responses, likely related to mechanical stretch, are better predictors of LV function and may represent novel targets for therapeutic intervention.
|Number of pages||9|
|State||Published - Dec 5 2008|
Bibliographical noteFunding Information:
The authors thank Kari B. Green-Church, PhD, from the OSU Campus Chemical Instrument Center for assistance with desmin identification, Angela C Cook, BS, for assistance with immunohistochemistry, and Brandon L. Schanbacher, MS, for assistance with image acquisition/analysis. This study was supported by grants from the National Heart Foundation/American Health Assistance Foundation, the Foundation for Anesthesia Education and Research/Society for Cardiovascular Anesthesiologists, and the American Heart Association. Additional support was provided by the Department of Anesthesiology, the Department of Surgery, the Center for Minimally-Invasive Surgery, and the Davis Scholarship Fund of The Ohio State University Medical Center.
Copyright 2009 Elsevier B.V., All rights reserved.
- Heart failure
ASJC Scopus subject areas
- Biochemistry, Genetics and Molecular Biology (all)
- Pharmacology, Toxicology and Pharmaceutics (all)