Cardiomyocyte stiffness in diastolic heart failure
Attila Borbély1, Jolanda van der Velden, Zoltán Papp
1Laboratory for Physiology, Institute for Cardiovascular Research, VUMC, Amsterdam, The Netherlands.
Circulation
|February 9, 2005
Summary
Diastolic heart failure (DHF) involves stiffer heart muscle cells, leading to impaired relaxation. Reduced protein phosphorylation may cause this stiffness, which can be reversed by protein kinase A (PKA).
Area of Science:
- Cardiology
- Molecular Biology
- Biophysics
Background:
- Diastolic heart failure (DHF), characterized by preserved left ventricular ejection fraction (EF), is increasingly recognized.
- The exact pathogenetic mechanisms of DHF are not fully understood due to limited myocardial biopsy material.
- This study analyzed endomyocardial biopsy samples from DHF patients to investigate myocardial characteristics.
Purpose of the Study:
- To analyze collagen volume fraction (CVF) and sarcomeric protein composition in DHF patients.
- To assess cellular contractile performance of isolated cardiomyocytes from DHF patients.
- To correlate myocardial properties with in vivo diastolic dysfunction.
Main Methods:
- Endomyocardial biopsy samples from DHF patients and controls were analyzed for CVF.
- Single cardiomyocytes were isolated and their contractile performance assessed.
- Mechanically isolated cardiomyocytes were activated with varying calcium concentrations to measure isometric force and resting tension (F(passive)).
Main Results:
- DHF patients exhibited higher CVFs compared to controls.
- Cardiomyocytes from DHF patients showed significantly higher resting tension (F(passive)) despite similar maximal force development.
- F(passive) and CVF together correlated better with elevated LV end-diastolic pressure (LVEDP) than either parameter alone.
Conclusions:
- DHF is associated with stiffer cardiomyocytes, evidenced by increased passive tension at a given sarcomere length.
- Increased F(passive) and CVF are key determinants of diastolic dysfunction in DHF.
- The ability of protein kinase A (PKA) to reduce F(passive) suggests reduced sarcomeric protein phosphorylation plays a role in DHF pathogenesis.
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