{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:42:52Z","timestamp":1790664172809,"version":"4.1.0"},"reference-count":32,"publisher":"American Physiological Society","issue":"12","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2014,12,15]]},"abstract":"<jats:p> Discordant myocardial growth and angiogenesis can explain left ventricular (LV) hypertrophy progressing toward heart failure with aging. Sirtuin 1 expression declines with age; therefore we explored the role played by angiogenesis and Sirtuin 1 in the development of cardiomyopathy. We compared the cardiac function of 10- to 15-wk-old (wo), 30\u201340 wo, and 61\u201370 wo endothelial Sirtuin 1-deleted (Sirt1<jats:sup>endo\u2212\/\u2212<\/jats:sup>) mice and their corresponding knockout controls (Sirt1<jats:sup>Flox\/Flox<\/jats:sup>). After 30\u201340 wk, Sirt1<jats:sup>endo\u2212\/\u2212<\/jats:sup> animals exhibited diastolic dysfunction (DD), decreased mRNA expression of Serca2a in the LV, and decreased capillary density compared with control animals despite a similar VEGFa mRNA expression. However, LV fibrosis and hypoxia-inducible factor (HIF)1\u03b1 expression were not different. The creation of a transverse aortic constriction (TAC) provoked more severe DD and LV fibrosis in Sirt1<jats:sup>endo\u2212\/\u2212<\/jats:sup> compared with control TAC animals. Although the VEGFa mRNA expression was not different and the protein expression of HIF1\u03b1 was higher in the Sirt1<jats:sup>endo\u2212\/\u2212<\/jats:sup> TAC animals, capillary density remained reduced. In cultured endothelial cells administration of Sirtuin 1 inhibitor decreased mRNA expression of VEGF receptors FLT 1 and FLK 1. Ex vivo capillary sprouting from aortic explants showed impaired angiogenic response to VEGF in the Sirt1<jats:sup>endo\u2212\/\u2212<\/jats:sup> mice. In conclusion, the data demonstrate 1) a defect in angiogenesis preceding development of DD; 2) dispensability of endothelial Sirtuin 1 under unstressed conditions and during normal aging; and 3) impaired angiogenic adaptation and aggravated DD in Sirt1<jats:sup>endo\u2212\/\u2212<\/jats:sup> mice challenged with LV overload. <\/jats:p>","DOI":"10.1152\/ajpheart.00281.2014","type":"journal-article","created":{"date-parts":[[2014,9,19]],"date-time":"2014-09-19T23:44:33Z","timestamp":1411170273000},"page":"H1691-H1704","source":"Crossref","is-referenced-by-count":54,"title":["Sirtuin 1 ablation in endothelial cells is associated with impaired angiogenesis and diastolic dysfunction"],"prefix":"10.1152","volume":"307","author":[{"given":"Julien","family":"Maizel","sequence":"first","affiliation":[{"name":"Medical Intensive Care Unit, Department of Nephrology and INSERM U-1088, University of Picardie, Amiens, France;"},{"name":"Department of Medicine, Renal Research Institute, New York Medical College, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandhya","family":"Xavier","sequence":"additional","affiliation":[{"name":"Department of Medicine, Renal Research Institute, New York Medical College, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Renal Research Institute, New York Medical College, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi Hua Sarah","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Medicine, Renal Research Institute, New York Medical College, Valhalla, New York"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Radovan","family":"Vasko","sequence":"additional","affiliation":[{"name":"Medical Intensive Care Unit, Department of Nephrology and INSERM U-1088, University of Picardie, Amiens, France;"},{"name":"Department of Nephrology and Rheumatology, University Medical Center, Gottingen, Germany; 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