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Right ventricular upregulation of the Ca(2+) binding protein S100A1 in chronic pulmonary hypertension
P Ehlermann1, A Remppis, O Guddat
1Medizinische Klinik II, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, D-23538, Lübeck, Germany.
Insights
S100A1 protein levels increase in the right ventricle during moderate pressure overload, suggesting an adaptive response to increased workload in cardiac hypertrophy. This finding offers new insights into myocardial calcium handling.
Area of Science:
- Cardiology
- Molecular Biology
- Physiology
Background:
- S100A1 protein influences calcium (Ca2+) release from the sarcoplasmic reticulum via ryanodine receptor interaction.
- Cardiac hypertrophy involves myocardial adaptation to increased workload, impacting cellular calcium homeostasis.
Purpose of the Study:
- To investigate S100A1 expression in a model of moderate right ventricular hypertrophy.
- To determine if S100A1 upregulation occurs in response to pressure overload in the early stages of cardiac hypertrophy.
Main Methods:
- A model of moderate pulmonary hypertension was induced in pigs via repeated embolization.
- Right ventricular tissue was analyzed for S100A1 expression, connective tissue content, and myocyte diameter.
- Expression levels of SERCA2a and phospholamban were also assessed.
Main Results:
- Pulmonary hypertension led to moderate right ventricular hypertrophy, characterized by increased connective tissue and myocyte size.
- S100A1 protein levels were significantly lower in the right ventricle compared to the left ventricle in control pigs.
- In pulmonary hypertension, S100A1 expression significantly increased in the hypertrophied right ventricles but remained unchanged in the left ventricle.
Conclusions:
- Moderate pressure overload induces a significant upregulation of S100A1 in the hypertrophied right ventricle.
- This upregulation of S100A1 may represent an adaptive mechanism to maintain myocardial calcium homeostasis under increased workload.
- SERCA2a and phospholamban expression remained unaltered, suggesting a specific role for S100A1 in this adaptive response.
Abstract:
The Ca(2+) binding protein S100A1 increases the Ca(2+) release from the sarcoplasmatic reticulum by interacting with the ryanodine receptor. In order to understand whether this effect might be operative in the early course of hypertrophy, when myocardium is able to meet increased workload, we investigated the expression of S100A1 in a model of moderate right ventricular hypertrophy. The pulmonary arteries of nine pigs were embolised three times with Sephadex G-50. After 70 days, all pigs showed a moderate pulmonary hypertension. Right ventricular tissue of embolised animals showed a significant increase of connective tissue and enlargement of myocyte diameters. In controls, we found a differential expression of S100A1 with significantly lower S100A1 protein levels in right ventricular compared to left ventricular tissue. In pulmonary hypertension, S100A1 expression increased significantly in hypertrophied right ventricles while it was unchanged in left ventricular tissue. No change was observed in the expression of SERCA2a and phospholamban. Our data show, for the first time, that moderate pressure overload results in an upregulation of S100A1. This may reflect an adaptive response of myocardial Ca(2+) homeostasis to a higher workload.