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Cardiac fibroblast proliferation rates and collagen expression mature early and are unaltered with advancing age
- Source :
- JCI Insight, Vol 5, Iss 24 (2020), JCI insight, vol 5, iss 24, JCI Insight
- Publication Year :
- 2020
- Publisher :
- American Society for Clinical investigation, 2020.
-
Abstract
- Cardiac fibrosis is a pathophysiologic hallmark of the aging heart, but little is known about how fibroblast proliferation and transcriptional programs change throughout the life span of the organism. Using EdU pulse labeling, we demonstrated that more than 50% of cardiac fibroblasts were actively proliferating in the first day of postnatal life. However, by 4 weeks, only 10% of cardiac fibroblasts were proliferating. By early adulthood, the fraction of proliferating cardiac fibroblasts further decreased to approximately 2%, where it remained throughout the rest of the organism's life. We observed that maximal changes in cardiac fibroblast transcriptional programs and, in particular, collagen and ECM gene expression both in the heart and cardiac fibroblast were maximal in the newly born and juvenile animal and decreased with organismal aging. Examination of DNA methylation changes both in the heart and in cardiac fibroblasts did not demonstrate significant changes in differentially methylated regions between young and old mice. Our observations demonstrate that cardiac fibroblasts attain a stable proliferation rate and transcriptional program early in the life span of the organism and suggest that phenotypic changes in the aging heart are not directly attributable to changes in proliferation rate or altered collagen expression in cardiac fibroblasts.
- Subjects :
- 0301 basic medicine
Aging
Cardiac fibrosis
Cells
Cardiology
lcsh:Medicine
Gene Expression
Biology
Inbred C57BL
Cardiovascular
Collagen Type I
Andrology
Extracellular matrix
03 medical and health sciences
Mice
0302 clinical medicine
Fibrosis
Gene expression
medicine
Animals
Juvenile animal
Fibroblast
Cells, Cultured
Cell Proliferation
Cultured
Myocardium
lcsh:R
Age Factors
Heart
General Medicine
Fibroblasts
medicine.disease
Cardiovascular disease
Mice, Inbred C57BL
030104 developmental biology
Differentially methylated regions
medicine.anatomical_structure
Heart Disease
Gene Expression Regulation
030220 oncology & carcinogenesis
DNA methylation
cardiovascular system
Medicine
Collagen
sense organs
Research Article
Subjects
Details
- Language :
- English
- ISSN :
- 23793708
- Volume :
- 5
- Issue :
- 24
- Database :
- OpenAIRE
- Journal :
- JCI Insight
- Accession number :
- edsair.doi.dedup.....4d31c9156c6fda561209f4a6c17fa894