TY - JOUR TI - Cardiovascular disease risk factors induce mesenchymal features and senescence in mouse cardiac endothelial cells AU - Hemanthakumar, Karthik Amudhala AU - Fang, Shentong AU - Anisimov, Andrey AU - Mäyränpää, Mikko I AU - Mervaala, Eero AU - Kivelä, Riikka T2 - eLife A2 - Bautch, Victoria L AB - 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-b 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 Serpinh1 (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. DA - 2021/03/04/ PY - 2021 DO - 10.7554/eLife.62678 DP - eLife VL - 10 SP - e62678 SN - 2050-084X UR - https://doi.org/10.7554/eLife.62678 Y2 - 2021/03/17/16:41:20 ER -