| First Author | Lisewski U | Year | 2020 |
| Journal | FASEB J | Volume | 34 |
| Issue | 8 | Pages | 10699-10719 |
| PubMed ID | 32584506 | Mgi Jnum | J:304211 |
| Mgi Id | MGI:6694419 | Doi | 10.1096/fj.202000013RR |
| Citation | Lisewski U, et al. (2020) Hypochlorhydria reduces mortality in heart failure caused by Kcne2 gene deletion. FASEB J 34(8):10699-10719 |
| abstractText | Heart failure (HF) is an increasing global health crisis, affecting 40 million people and causing 50% mortality within 5 years of diagnosis. 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-specific germline deletion in mice of potassium channel beta subunit-encoding Kcne2 (Kcne2(CS-/-) ) causes dilated cardiomyopathy and terminal HF (median longevity, 28 weeks). Mice with global Kcne2 deletion (Kcne2(Glo-/-) ) exhibit multiple HF risk factors, yet, paradoxically survived over twice as long as Kcne2(CS-/-) mice. Global Kcne2 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-pump inhibitor omeprazole similarly altered the microbiome and delayed terminal HF in Kcne2(CS-/-) mice, increasing survival 10-fold at 44 weeks. Thus, genetic or pharmacologic induction of hypochlorhydria and decreased gut Bacteroidales species are associated with lifespan extension in a novel HF model. |
