Hypoxia Attenuates Pressure Overload‐Induced Heart Failure

dc.contributor.authorFroese, Natali
dc.contributor.authorSzaroszyk, Malgorzata
dc.contributor.authorGaluppo, Paolo
dc.contributor.authorVisker, Joseph R.
dc.contributor.authorWerlein, Christopher
dc.contributor.authorKorf‐Klingebiel, Mortimer
dc.contributor.authorBerliner, Dominik
dc.contributor.authorReboll, Marc R.
dc.contributor.authorHamouche, Rana
dc.contributor.authorGegel, Simona
dc.contributor.authorWang, Yong
dc.contributor.authorHofmann, Winfried
dc.contributor.authorTang, Ming
dc.contributor.authorGeffers, Robert
dc.contributor.authorWende, Adam R.
dc.contributor.authorKühnel, Mark P.
dc.contributor.authorJonigk, Danny D.
dc.contributor.authorHansmann, Georg
dc.contributor.authorWollert, Kai C.
dc.contributor.authorAbel, E. Dale
dc.contributor.authorDrakos, Stavros G.
dc.contributor.authorBauersachs, Johann
dc.contributor.authorRiehle, Christian
dc.date.accessioned2024-04-23T11:31:27Z
dc.date.available2024-04-23T11:31:27Z
dc.date.issued2024-02-06en_US
dc.date.updated2024-04-17T11:51:06Z
dc.description.abstract<sec xmlns:mml="http://www.w3.org/1998/Math/MathML" sec-type="background" id="jah39261-sec-0001" xml:lang="en"> <title>Background</title> <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)–induced heart failure. We furthermore aimed to test that overlapping mechanisms promote cardiac recovery in heart failure patients following left ventricular assist device‐mediated mechanical unloading and circulatory support.</p> </sec><sec xmlns:mml="http://www.w3.org/1998/Math/MathML" id="jah39261-sec-0002" xml:lang="en"> <title>Methods and Results</title> <p xml:lang="en">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‐inducible factor)‐1α–mediated angiogenesis, attenuated induction of genes associated with pathological remodeling, and preserved metabolic gene expression as identified by RNA sequencing. Furthermore, LVPO decreased <italic toggle="no">Tbx5</italic> and increased <italic toggle="no">Hsd11b1</italic> mRNA expression under normoxic conditions, which was attenuated under hypoxic conditions and may induce additional hypoxia‐mediated cardioprotective effects. Analysis of samples from patients with advanced heart failure that demonstrated left ventricular assist device–mediated myocardial recovery revealed a similar expression pattern for <italic toggle="no">TBX5</italic> and <italic toggle="no">HSD11B1</italic> as observed in HxTAC hearts.</p> </sec><sec xmlns:mml="http://www.w3.org/1998/Math/MathML" id="jah39261-sec-0003" xml:lang="en"> <title>Conclusions</title> <p xml:lang="en">Hypoxia attenuates LVPO‐induced 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‐mediated cardioprotective mechanisms and therapeutic targets that attenuate LVPO‐induced heart failure and mediate cardiac recovery following mechanical circulatory support.</p> </sec>
dc.description.sponsorshipGerman Heart Foundation http://dx.doi.org/10.13039/501100005971
dc.description.sponsorshipGerman Research Foundation http://dx.doi.org/10.13039/501100001659
dc.description.sponsorshipClinical Research Unit
dc.description.sponsorshipAmerican Heart Association Heart Failure Strategically Focused Research Network
dc.description.sponsorshipNational Heart, Lung, and Blood Institute http://dx.doi.org/10.13039/100000050
dc.description.sponsorshipNora Eccles Treadwell Foundation http://dx.doi.org/10.13039/100017995
dc.identifier.citationJournal of the American Heart Association 13.3 (2024). DOI:10.1161/JAHA.123.033553
dc.identifier.doi10.1161/JAHA.123.033553
dc.identifier.issn2047-9980
dc.identifier.otherJAH3
dc.identifier.otherahaoa
dc.identifier.urihttps://open.fau.de/handle/openfau/30879
dc.language.isoen
dc.publisher
dc.rights.uriThis is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
dc.subjectcardiac hypertrophy
dc.subjectcardiac remodeling
dc.subjecthypoxia
dc.subjectleft ventricular assist device
dc.subjectpressure overload
dc.titleHypoxia Attenuates Pressure Overload‐Induced Heart Failure
dc.typearticle
local.document.pageend
local.document.pagestart
local.journal.issue3
local.journal.titleJournal of the American Heart Association
local.journal.volume13
local.sendToDnbfree*
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