{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T13:42:37Z","timestamp":1788183757966,"version":"build-2803163510"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2024,2,6]]},"abstract":"<jats:sec sec-type=\"background\" xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Alveolar hypoxia is protective in the context of cardiovascular and ischemic heart disease; however, the underlying mechanisms are incompletely understood. The present study sought to test the hypothesis that hypoxia is cardioprotective in left ventricular pressure overload (LVPO)\u2013induced heart failure. We furthermore aimed to test that overlapping mechanisms promote cardiac recovery in heart failure patients following left ventricular assist device\u2010mediated mechanical unloading and circulatory support.<\/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              We established a novel murine model of combined chronic alveolar hypoxia and LVPO following transverse aortic constriction (HxTAC). The HxTAC model is resistant to cardiac hypertrophy and the development of heart failure. The cardioprotective mechanisms identified in our HxTAC model include increased activation of HIF (hypoxia\u2010inducible factor)\u20101\u03b1\u2013mediated angiogenesis, attenuated induction of genes associated with pathological remodeling, and preserved metabolic gene expression as identified by RNA sequencing. Furthermore, LVPO decreased\n              <jats:italic>Tbx5<\/jats:italic>\n              and increased\n              <jats:italic>Hsd11b1<\/jats:italic>\n              mRNA expression under normoxic conditions, which was attenuated under hypoxic conditions and may induce additional hypoxia\u2010mediated cardioprotective effects. Analysis of samples from patients with advanced heart failure that demonstrated left ventricular assist device\u2013mediated myocardial recovery revealed a similar expression pattern for\n              <jats:italic>TBX5<\/jats:italic>\n              and\n              <jats:italic>HSD11B1<\/jats:italic>\n              as observed in HxTAC hearts.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">Hypoxia attenuates LVPO\u2010induced heart failure. Cardioprotective pathways identified in the HxTAC model might also contribute to cardiac recovery following left ventricular assist device support. These data highlight the potential of our novel HxTAC model to identify hypoxia\u2010mediated cardioprotective mechanisms and therapeutic targets that attenuate LVPO\u2010induced heart failure and mediate cardiac recovery following mechanical circulatory support.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.123.033553","type":"journal-article","created":{"date-parts":[[2024,1,31]],"date-time":"2024-01-31T11:19:41Z","timestamp":1706699981000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":15,"title":["Hypoxia Attenuates Pressure Overload\u2010Induced Heart Failure"],"prefix":"10.1161","volume":"13","author":[{"given":"Natali","family":"Froese","sequence":"first","affiliation":[{"name":"Department of Cardiology and Angiology Hannover Medical School Hannover 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