期刊
ELIFE
卷 10, 期 -, 页码 -出版社
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.62678
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- Jenny ja Antti Wihurin Rahasto
- Academy of Finland [297245]
- Sydantutkimussaatio
- Sigrid Juseliuksen Satio
- Suomen Kulttuurirahasto
- Suomen Laaketieteen Saatio
- Biomedicum Helsinki-saatio
- Aarne Koskelon Saatio
- Academy of Finland (AKA) [297245, 297245] Funding Source: Academy of Finland (AKA)
The study found that risk factors for CVD such as aging, obesity, and hypertension significantly impact the gene expression of cardiac endothelial cells, resulting in inflammatory, senescence, and mesenchymal features. Exercise training can alleviate these effects, highlighting the importance of exercise in preventing CVD.
Aging, obesity, hypertension, and physical inactivity are major risk factors for endothelial dysfunction and cardiovascular disease (CVD). We applied fluorescence-activated cell sorting (FACS), RNA sequencing, and bioinformatic methods to investigate the common effects of CVD risk factors in mouse cardiac endothelial cells (ECs). Aging, obesity, and pressure overload all upregulated pathways related to TGF-beta signaling and mesenchymal gene expression, inflammation, vascular permeability, oxidative stress, collagen synthesis, and cellular senescence, whereas exercise training attenuated most of the same pathways. We identified collagen chaperone Serpinhl (also called as Hsp47) to be significantly increased by aging and obesity and repressed by exercise training. Mechanistic studies demonstrated that increased SERPINH1 in human ECs induced mesenchymal properties, while its silencing inhibited collagen deposition. Our data demonstrate that CVD risk factors significantly remodel the transcriptomic landscape of cardiac ECs inducing inflammatory, senescence, and mesenchymal features. SERPINH1 was identified as a potential therapeutic target in ECs.
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