{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T06:53:23Z","timestamp":1791356003306,"version":"4.3.1"},"reference-count":45,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,10,6]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">The pathogenesis of thoracic aortic dissection (TAD) involves phenotypic switching of vascular smooth muscle cells (VSMCs) and VSMCs apoptosis. PXR (pregnane X receptor) is a known regulator of apoptosis. The mechanistic role of PXR in the pathogenesis of TAD remains elusive.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Microarray data sets related to TAD were obtained from the Gene Expression Omnibus database to identify differentially expressed genes. Four\u2010week\u2010old male\n                      <jats:italic toggle=\"no\">Pxr<\/jats:italic>\n                      \u2010overexpressing mice, beta carotene\u2013treated mice, and\n                      <jats:italic toggle=\"no\">Ldha<\/jats:italic>\n                      \u2010knockdown mice were administered \u03b2\u2010aminopropionitrile (1\u2009g\/kg per day) in drinking water for 4\u2009weeks, followed by intraperitoneal injection of angiotensin II (1.44\u2009mg\/kg 3 times daily) for 3\u2009days to induce TAD. Lactate concentration and lactate dehydrogenase activity were measured using commercially available assay kits. Apoptosis was assessed by TUNEL staining. VSMC phenotype transformation was detected by quantitative real\u2010time polymerase chain reaction, immunofluorescence, and western blot.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Microarray analysis of data sets from the Gene Expression Omnibus revealed downregulated PXR expression in aortic tissues from TAD patients. Consistently, reduced PXR expression was observed in aortic tissues from both TAD patients and \u03b2\u2010aminopropionitrile\u2013induced TAD mice. \u03b2\u2010Aminopropionitrile\u2013induced TAD progression was significantly ameliorated in mice with PXR overexpression or activation. PXR activation effectively suppressed VSMCs phenotypic switching. It also inhibited LDHA expression, thereby reducing lactate accumulation, attenuating VSMC apoptosis, and ultimately alleviating TAD progression. In line with these findings, \u03b2\u2010aminopropionitrile\u2013induced TAD progression was significantly ameliorated in\n                      <jats:italic toggle=\"no\">Ldha<\/jats:italic>\n                      \u2010knockdown mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">PXR signaling may represent a novel target for the prevention and treatment of TAD.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.125.047767","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T04:36:16Z","timestamp":1790310976000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Pregnane X Receptor Activation Attenuates Aortic Dissection by Suppressing Lactate Dehydrogenase A\u2013Mediated Lactate Metabolism"],"prefix":"10.1161","volume":"15","author":[{"given":"Lele","family":"Tang","sequence":"first","affiliation":[{"name":"Fujian Medical University Union Hospital","place":["Fuzhou, China"]},{"name":"Fujian Province University","place":["Fuzhou, China"]},{"name":"Fujian Province University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoyu","family":"Li","sequence":"additional","affiliation":[{"name":"Fujian Medical University Union Hospital","place":["Fuzhou, China"]},{"name":"Fujian Province University","place":["Fuzhou, China"]},{"name":"Fujian Province University","place":["Fuzhou, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukun","family":"Chen","sequence":"additional","affiliation":[{"name":"Fujian Medical University Union Hospital","place":["Fuzhou, China"]},{"name":"Fujian Province University","place":["Fuzhou, China"]},{"name":"Fujian Province University","place":["Fuzhou, 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