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Updated: Jul 11, 2025
Methods for the Isolation, Culture, and Functional Characterization of Sinoatrial Node Myocytes from Adult Mice
Published on: October 23, 2016
Transcriptome of Left Ventricle and Sinoatrial Node in Young and Old C57 Mice
Jia-Hua Qu1, Kirill V Tarasov1, Yelena S Tarasova1
1Laboratory of Cardiovascular Science, Intramural Research Program, National Institute on Aging, National Institutes of Health, Baltimore, MD 21224, USA.
Insights
Aging impacts heart function by altering cells in the sinoatrial node (SAN) and left ventricle (LV). This study compares molecular changes in these aging heart cells to find new cardiovascular disease (CVD) targets.
Area of Science:
- Cardiovascular Biology
- Aging Research
- Molecular Cardiology
Background:
- Advancing age is the primary risk factor for cardiovascular diseases (CVDs).
- Heart function relies on sinoatrial node (SAN) and left ventricle (LV) cells, which decline with age, increasing CVD risk.
- Molecular differences in age-associated changes between SAN and LV cells remain uncharacterized at the omics level.
Purpose of the Study:
- To compare age-associated molecular changes in SAN and LV cells using deep RNA sequencing.
- To identify chamber-specific gene expression patterns related to aging, energy production, longevity, and CVD markers.
- To predict upstream regulatory activities impacting age-related cardiac dysfunction.
Main Methods:
- Deep RNA sequencing of young and old SAN and LV samples.
- Comprehensive bioinformatic analyses, including differential gene expression and pathway analysis.
- Analysis of genes related to cardiomyocyte contraction, post-transcriptional processing, longevity pathways (KEGG), GenAge database entries, and CVD markers.
Main Results:
- Detailed profiling of gene expression differences between LV and SAN cells.
- Identification of concordant and discordant age-associated gene expression changes specific to each heart chamber.
- Prediction of transcription regulators and miRNA activities influencing age-related cardiac changes.
Conclusions:
- This study provides a comprehensive molecular comparison of aging in SAN and LV cells.
- Findings enhance understanding of heart function regulation during aging.
- The results offer potential gene-specific therapeutic targets for age-related CVDs.
Abstract:
Advancing age is the most important risk factor for cardiovascular diseases (CVDs). Two types of cells, within the heart pacemaker, sinoatrial node (SAN), and within the left ventricle (LV), control two crucial characteristics of heart function, heart beat rate and contraction strength. As age advances, the heart's structure becomes remodeled, and SAN and LV cell functions deteriorate, thus increasing the risk for CVDs. However, the different molecular features of age-associated changes in SAN and LV cells have never been compared in omics scale in the context of aging. We applied deep RNA sequencing to four groups of samples, young LV, old LV, young SAN and old SAN, followed by numerous bioinformatic analyses. In addition to profiling the differences in gene expression patterns between the two heart chambers (LV vs. SAN), we also identified the chamber-specific concordant or discordant age-associated changes in: (1) genes linked to energy production related to cardiomyocyte contraction, (2) genes related to post-transcriptional processing, (3) genes involved in KEGG longevity regulating pathway, (4) prolongevity and antilongevity genes recorded and curated in the GenAge database, and (5) CVD marker genes. Our bioinformatic analysis also predicted the regulation activities and mapped the expression of upstream regulators including transcription regulators and post-transcriptional regulator miRNAs. This comprehensive analysis promotes our understanding of regulation of heart functions and will enable discovery of gene-specific therapeutic targets of CVDs in advanced age.
