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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-\u03b2 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\n                    <jats:italic>Serpinh1<\/jats:italic>\n                    (also called as\n                    <jats:italic>Hsp47<\/jats:italic>\n                    ) 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.\n                  <\/jats:p>","DOI":"10.7554\/elife.62678","type":"journal-article","created":{"date-parts":[[2021,3,4]],"date-time":"2021-03-04T08:00:45Z","timestamp":1614844845000},"update-policy":"https:\/\/doi.org\/10.7554\/elife.62678","source":"Crossref","is-referenced-by-count":38,"title":["Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells"],"prefix":"10.7554","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6151-1005","authenticated-orcid":true,"given":"Karthik Amudhala","family":"Hemanthakumar","sequence":"first","affiliation":[{"name":"Wihuri Research Institute, Helsinki, Finland"},{"name":"Stem cells and Metabolism Research Program, Research Programs Unit, Faculty of Medicine, University of Helsinki, Helsinki, 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