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Decreased expression of calmodulin mRNA in human end-stage heart failure
C D Jeck1, R Zimmermann, J Schaper
1Department of Experimental Cardiology, Max-Planck Instutute for Physiological and Clinical Research, Bad Nauheim, Germany.
Abstract:
Calmodulin (CaM) is the primary Ca2+ regulatory protein in cardiac cells, thus alterations in calmodulin would greatly influence the contractile response and may play a role in the abnormal calcium handling observed in human heart failure. We used Northern blot analysis to determine changes in calmodulin mRNA expression in left ventricular tissues isolated from 20 failing and four control human hearts. Only hearts with failure due to idiopathic dilated cardiomyopathy (DCM) or ischaemic heart disease (IHD) were studied. A human calmodulin cDNA probe 95% homologous to Type 3 CaM was used, which hybridized to a single 2.3 kb mRNA. CaM mRNA levels were expressed as a function of total RNA, as determined by hybridization to an 18S cDNA probe, and as a function of myocyte specific mRNA, as determined by hybridization to a myosin heavy chain (MHC) cDNA probe. In both DCM and IHD, CaM mRNA expression relative to total RNA (CaM/18S), was significantly decreased (45% and 61%, respectively) compared to control hearts. CaM mRNA expression in DCM tissues was also significantly decreased (45%) relative to myocyte specific mRNA (CaM/MHC), when compared to control hearts. In IHD, CaM mRNA was not significantly decreased in relation to myocyte specific mRNA, which suggests a greater loss of myocytes or contractile proteins in IHD as compared with DCM. The decreased expressed of CaM mRNA observed in failing hearts could affect many Ca(2+)-dependent processes, and contribute to the inability of these hearts to handle Ca2+ in a viable manner.
Insights
Calmodulin mRNA expression is significantly decreased in human heart failure, impacting calcium handling. This reduction was more pronounced relative to total RNA than myocyte-specific mRNA, suggesting cell loss in ischemic heart disease.
Area of Science:
- Cardiology
- Molecular Biology
- Biochemistry
Background:
- Calmodulin (CaM) is a key calcium (Ca2+) regulatory protein in cardiac cells.
- Altered CaM function can influence cardiac contractility and calcium handling, potentially contributing to heart failure.
Purpose of the Study:
- To investigate changes in calmodulin mRNA expression in human heart failure.
- To compare CaM mRNA levels in idiopathic dilated cardiomyopathy (DCM) and ischemic heart disease (IHD) versus control hearts.
Main Methods:
- Northern blot analysis was used to quantify CaM mRNA levels in left ventricular tissues.
- CaM mRNA was normalized to both total RNA (18S rRNA) and myocyte-specific mRNA (myosin heavy chain, MHC).
Main Results:
- Calmodulin mRNA expression relative to total RNA was significantly decreased in both DCM (45%) and IHD (61%) compared to controls.
- In DCM, CaM mRNA relative to myocyte-specific mRNA also decreased significantly (45%).
- In IHD, CaM mRNA relative to myocyte-specific mRNA showed no significant decrease, suggesting greater myocyte loss.
Conclusions:
- Decreased calmodulin mRNA expression in failing human hearts may impair Ca2+-dependent processes.
- The findings suggest differential mechanisms of myocyte loss or protein reduction in DCM and IHD.