{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:33:47Z","timestamp":1790717627521,"version":"4.1.0"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2015,1,30]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Cardiac dysfunction developing in response to chronic pressure overload is associated with apoptotic cell death and myocardial vessel rarefaction. We examined whether deletion of tumor suppressor p53 in endothelial cells may prevent the transition from cardiac hypertrophy to heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Mice with endothelial\u2010specific deletion of p53 (End.p53\u2010\n                      <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>\n                      ) were generated by crossing p53\n                      <jats:sub>fl\/fl<\/jats:sub>\n                      mice with mice expressing Cre recombinase under control of an inducible Tie2 promoter. Cardiac hypertrophy was induced by transverse aortic constriction. Serial echocardiography measurements revealed improved cardiac function in End.p53\u2010\n                      <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>\n                      mice that also exhibited better survival. Cardiac hypertrophy was associated with increased p53 levels in End.p53\u2010\n                      <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n                      controls, whereas banded hearts of End.p53\u2010\n                      <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>\n                      mice exhibited lower numbers of apoptotic endothelial and non\u2010endothelial cells and altered\n                      <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                      levels of genes regulating cell cycle progression (p21), apoptosis (Puma), or proliferation (Pcna). A higher cardiac capillary density and improved myocardial perfusion was observed, and pharmacological inhibition or genetic deletion of p53 also promoted endothelial sprouting in vitro and new vessel formation following hindlimb ischemia in vivo. Hearts of End.p53\u2010\n                      <jats:styled-content style=\"fixed-case\">KO<\/jats:styled-content>\n                      mice exhibited markedly less fibrosis compared with End.p53\u2010\n                      <jats:styled-content style=\"fixed-case\">WT<\/jats:styled-content>\n                      controls, and lower\n                      <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content>\n                      levels of p53\u2010regulated genes involved in extracellular matrix production and turnover (eg, Bmp\u20107, Ctgf, or Pai\u20101), or of transcription factors involved in controlling mesenchymal differentiation were observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Our analyses reveal that accumulation of p53 in endothelial cells contributes to blood vessel rarefaction and fibrosis during chronic cardiac pressure overload and suggest that endothelial cells may be a therapeutic target for preserving cardiac function during hypertrophy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.115.001770","type":"journal-article","created":{"date-parts":[[2015,2,26]],"date-time":"2015-02-26T07:09:24Z","timestamp":1424934564000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":135,"title":["Endothelial p53 Deletion Improves Angiogenesis and Prevents Cardiac Fibrosis and Heart Failure Induced by Pressure Overload in Mice"],"prefix":"10.1161","volume":"4","author":[{"given":"Rajinikanth","family":"Gogiraju","sequence":"first","affiliation":[{"name":"Department of Cardiology and Pneumology, University Medical Center G\u00f6ttingen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingbo","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of 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