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A fuller understanding of the genetic and environmental factors underlying HF, and novel therapeutic approaches to address it, are urgently warranted. Here, we discovered that cardiac\u2010specific germline deletion in mice of potassium channel \u03b2 subunit\n                    <jats:italic>\u2010<\/jats:italic>\n                    encoding\n                    <jats:italic>Kcne2<\/jats:italic>\n                    (\n                    <jats:italic>Kcne2<\/jats:italic>\n                    <jats:sup>CS\u2212\/\u2212<\/jats:sup>\n                    ) causes dilated cardiomyopathy and terminal HF (median longevity, 28\u00a0weeks). Mice with global\n                    <jats:italic>Kcne2<\/jats:italic>\n                    deletion (\n                    <jats:italic>Kcne2<\/jats:italic>\n                    <jats:sup>Glo\u2212\/\u2212<\/jats:sup>\n                    ) exhibit multiple HF risk factors, yet, paradoxically survived over twice as long as\n                    <jats:italic>Kcne2<\/jats:italic>\n                    <jats:sup>CS\u2212\/\u2212<\/jats:sup>\n                    mice. Global\n                    <jats:italic>Kcne2<\/jats:italic>\n                    deletion, which inhibits gastric acid secretion, reduced the relative abundance of species within Bacteroidales, a bacterial order that positively correlates with increased lifetime risk of human cardiovascular disease. Strikingly, the proton\u2010pump inhibitor omeprazole similarly altered the microbiome and delayed terminal HF in\n                    <jats:italic>Kcne2<\/jats:italic>\n                    <jats:sup>CS\u2212\/\u2212<\/jats:sup>\n                    mice, increasing survival 10\u2010fold at 44\u00a0weeks. Thus, genetic or pharmacologic induction of hypochlorhydria and decreased gut Bacteroidales species are associated with lifespan extension in a novel HF model.\n                  <\/jats:p>","DOI":"10.1096\/fj.202000013rr","type":"journal-article","created":{"date-parts":[[2020,7,29]],"date-time":"2020-07-29T14:24:42Z","timestamp":1596032682000},"page":"10699-10719","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hypochlorhydria reduces mortality in heart failure caused by\n                    <i>Kcne2<\/i>\n                    gene deletion"],"prefix":"10.1096","volume":"34","author":[{"given":"Ulrike","family":"Lisewski","sequence":"first","affiliation":[{"name":"Experimental and Clinical Research Center Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clemens","family":"K\u00f6hncke","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center Berlin Germany"},{"name":"Department of Cardiology Campus Virchow \u2013 Universit\u00e4tsmedizin Berlin Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonhard","family":"Schleussner","sequence":"additional","affiliation":[{"name":"Experimental and Clinical Research Center Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina","family":"Purf\u00fcrst","sequence":"additional","affiliation":[{"name":"Electron Microscopy Core Facility Max\u2010Delbr\u00fcck\u2010Center for Molecular Medicine Berlin Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soo Min","family":"Lee","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory Department of Physiology and Biophysics School of Medicine University of California Irvine CA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angele","family":"De Silva","sequence":"additional","affiliation":[{"name":"Bioelectricity Laboratory 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