{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T15:38:39Z","timestamp":1791214719193,"version":"4.1.0"},"reference-count":32,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2011,5,1]],"date-time":"2011-05-01T00:00:00Z","timestamp":1304208000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,5,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>Inhibitors of histone deacetylases (HDACs) reduce pressure-overload\u2013induced left ventricular hypertrophy and dysfunction, but their effects on right ventricular (RV) adaptation to pressure overload are unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Determine the effect of the broad-spectrum HDAC inhibitors trichostatin A (TSA) and valproic acid (VPA) on RV function and remodeling after pulmonary artery banding (PAB) in rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Chronic progressive RV pressure-overload was induced in rats by PAB. After establishment of adaptive RV hypertrophy 4 weeks after surgery, rats were treated for 2 weeks with vehicle, TSA, or VPA. RV function and remodeling were determined using echocardiography, invasive hemodynamic measurements, immunohistochemistry, and molecular analyses after 2 weeks of HDAC inhibition. The effects of TSA were determined on the expression of proangiogenic and prohypertrophic genes in human myocardial fibroblasts and microvascular endothelial cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>TSA treatment did not prevent the development of RV hypertrophy and was associated with RV dysfunction, capillary rarefaction, fibrosis, and increased rates of myocardial cell death. Similar results were obtained with the structurally unrelated HDAC inhibitor VPA. With TSA treatment, a reduction was found in expression of vascular endothelial growth factor and angiopoietin-1, which proteins are involved in vascular adaptation to pressure-overload. TSA dose-dependently suppressed vascular endothelial growth factor, endothelial nitric oxide synthase, and angiopoietin-1 expression in cultured myocardial endothelial cells, which effects were mimicked by selective gene silencing of several class I and II HDACs.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>HDAC inhibition is associated with dysfunction and worsened remodeling of the pressure-overloaded RV. The detrimental effects of HDAC inhibition on the pressure-overloaded RV may come about via antiangiogenic or proapoptotic effects.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.201007-1106oc","type":"journal-article","created":{"date-parts":[[2011,2,4]],"date-time":"2011-02-04T22:37:28Z","timestamp":1296859048000},"page":"1402-1410","source":"Crossref","is-referenced-by-count":141,"title":["Suppression of Histone Deacetylases Worsens Right Ventricular Dysfunction after Pulmonary Artery Banding in Rats"],"prefix":"10.1093","volume":"183","author":[{"given":"Harm J.","family":"Bogaard","sequence":"first","affiliation":[{"name":"Division of Pulmonary and Critical Care, and"},{"name":"Department of Pulmonary Medicine, VU University Medical Center, Amsterdam, The Netherlands; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiro","family":"Mizuno","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayser A. Al","family":"Hussaini","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Toldo","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine and Victoria Johnson Center for Lung Research, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Abbate","sequence":"additional","affiliation":[{"name":"Division of Cardiology, Department of Medicine and Victoria Johnson Center for Lung Research, Virginia Commonwealth University, Richmond, Virginia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donatas","family":"Kraskauskas","sequence":"additional","affiliation":[{"name":"Division of Pulmonary and Critical Care, 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