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Assessment of Sarcoplasmic Reticulum Calcium Reserve and Intracellular Diastolic Calcium Removal in Isolated Ventricular Cardiomyocytes
Published on: September 18, 2017
Cardiac Resynchronization and Circulating Markers of Sarcoplasmic Reticulum Calcium Handling and Sudden Death Risk
Ning Jiang1, Anyu Zhou2, Hafiz Imran2
1Lifespan Cardiovascular Institute, Brown University, Providence, Rhode Island, USA.
Insights
Cardiac resynchronization therapy (CRT) improves heart function by altering circulating biomarkers. CRT reduces nonfunctional sodium channels and enhances SERCA2a expression, potentially lowering sudden death risk.
Area of Science:
- Cardiology
- Molecular Biology
- Biomarkers
Background:
- Cardiac resynchronization therapy (CRT) is known to improve heart function and reduce arrhythmias.
- Heart failure is associated with impaired calcium handling and altered sodium channel function.
- Reduced sarco/endoplasmic reticulum calcium adenosine triphosphatase 2a (SERCA2a) expression is linked to diminished cardiac contractility.
Purpose of the Study:
- To investigate the effect of CRT on circulating markers of calcium handling.
- To determine if CRT alters biomarkers associated with sudden cardiac death risk.
- To explore the relationship between CRT and specific cardiac gene expression in circulation.
Main Methods:
- Analysis of circulating messenger RNA (mRNA) splicing variants of cardiac sodium channels.
- Quantification of SERCA2a mRNA expression levels in patients.
- Comparison of biomarker levels between patients with and without CRT.
Main Results:
- CRT was associated with a decreased proportion of nonfunctional cardiac sodium channel mRNA variants.
- Patients receiving CRT showed improved SERCA2a mRNA expression compared to baseline.
- No significant improvement in these biomarkers was observed in patients without CRT.
Conclusions:
- CRT may improve cardiac function and reduce arrhythmic risk by favorably altering circulating cardiac biomarkers.
- Changes in sodium channel variants and SERCA2a expression provide potential mechanistic insights into CRT's benefits.
- Circulating mRNA markers could serve as indicators of CRT response and therapeutic efficacy.
Abstract:
Cardiac resynchronization therapy (CRT) can improve heart function and decrease arrhythmic events. We tested whether CRT altered circulating markers of calcium handling and sudden death risk. Circulating cardiac sodium channel messenger RNA (mRNA) splicing variants indicate arrhythmic risk, and a reduction in sarco/endoplasmic reticulum calcium adenosine triphosphatase 2a (SERCA2a) is thought to diminish contractility in heart failure. CRT was associated with a decreased proportion of circulating, nonfunctional sodium channels and improved SERCA2a mRNA expression. Patients without CRT did not have improvement in the biomarkers. These changes might explain the lower arrhythmic risk and improved contractility associated with CRT.
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