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Published on: August 1, 2016
Relation between myocardial function and expression of sarcoplasmic reticulum Ca(2+)-ATPase in failing and nonfailing
G Hasenfuss1, H Reinecke, R Studer
1Medizinische Klinik III, Universität Freiburg, Germany.
Insights
Reduced sarcoplasmic reticulum Ca(2+)-ATPase in heart failure impairs myocardial function. Lower SR Ca(2+)-ATPase protein levels correlated with decreased calcium uptake and force-frequency relation in failing human hearts.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- Sarcoplasmic reticulum (SR) Ca(2+)-ATPase expression is reduced in human heart failure.
- The functional impact of diminished SR Ca(2+)-ATPase in failing myocardium remains unclear.
Purpose of the Study:
- To investigate the relationship between myocardial function and SR Ca(2+)-ATPase protein levels in nonfailing and failing human hearts.
- To assess the functional consequences of reduced SR Ca(2+)-ATPase in dilated and ischemic cardiomyopathy.
Main Methods:
- Isometric contraction force-frequency relation measurements in human myocardial muscle strips.
- Quantification of SR Ca(2+)-ATPase protein levels normalized to total protein or myosin.
- Measurement of SR Ca2+ uptake in heart homogenates.
Main Results:
- Failing myocardium exhibited impaired force-frequency relation, with no tension increase at higher stimulation rates.
- SR Ca(2+)-ATPase protein levels were significantly reduced in both dilated (36%) and ischemic (32%) cardiomyopathy.
- Reduced SR Ca(2+)-ATPase protein levels strongly correlated with decreased SR Ca2+ uptake (r = .70).
Conclusions:
- Diminished SR Ca(2+)-ATPase expression is a key feature of human heart failure.
- Reduced SR Ca(2+)-ATPase contributes to impaired myocardial contractility and calcium handling in failing hearts.
Abstract:
Expression of sarcoplasmic reticulum (SR) Ca(2+)-ATPase was shown to be reduced in failing human myocardium. The functional relevance of this finding, however, is not known. We investigated the relation between myocardial function and protein levels of SR Ca(2+)-ATPase in nonfailing human myocardium (8 muscle strips from 4 hearts) and in myocardium from end-stage failing hearts with dilated (10 muscle strips from 9 hearts) or ischemic (7 muscle strips from 5 hearts) cardiomyopathy. Myocardial function was evaluated by the force-frequency relation in isometrically contracting muscle strip preparations (37 degrees C, 30 to 180 min-1). In nonfailing myocardium, twitch tension rose with increasing rates of stimulation and was 76% higher at 120 min-1 compared with 30 min-1 (P < .02). In failing myocardium, there was no significant increase in average tension at stimulation rates above 30 min-1. At 120 min-1, twitch tension was decreased by 59% (P < .05) in dilated cardiomyopathy and 76% (P < .05) in ischemic cardiomyopathy compared with nonfailing myocardium. Protein levels of SR Ca(2+)-ATPase, normalized per total protein or per myosin, were reduced by 36% (P < .02) or 32% (P < .05), respectively, in failing compared with nonfailing myocardium. SR Ca(2+)-ATPase protein levels were closely related to SR Ca2+ uptake, measured in homogenates from the same hearts (r = .70, n = 16, and P < .005).(ABSTRACT TRUNCATED AT 250 WORDS)
