@article{4650,
  keywords = {Humans, Energy Metabolism, Heart, Amino Acids, Branched-Chain, Heart Failure, Blood Pressure},
  author = {Danielle Murashige and Jae Jung and Michael Neinast and Michael Levin and Qingwei Chu and Jonathan Lambert and Joanne Garbincius and Boa Kim and Atsushi Hoshino and Ingrid Marti-Pamies and Kendra McDaid and Swapnil Shewale and Emily Flam and Steven Yang and Emilia Roberts and Li Li and Michael Morley and Kenneth Bedi and Matthew Hyman and David Frankel and Kenneth Margulies and Richard Assoian and John Elrod and Cholsoon Jang and Joshua Rabinowitz and Zoltan Arany},
  title = {Extra-cardiac BCAA catabolism lowers blood pressure and protects from heart failure.},
  abstract = { <p>Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protective in models of heart failure (HF). How protection occurs remains unclear, although a causative block in cardiac BCAA oxidation is widely assumed. Here, we use in~vivo isotope infusions to show that cardiac BCAA oxidation in fact increases, rather than decreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does not protect from HF even though systemic activation does. Lowering plasma and cardiac BCAAs also fails to confer significant protection, suggesting alternative mechanisms of protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP), a known cardioprotective mechanism. BP lowering occurred independently of nitric oxide and reflected vascular resistance to adrenergic constriction. Mendelian randomization studies revealed that elevated plasma BCAAs portend higher BP in humans. Together, these data indicate that BCAA oxidation lowers vascular resistance, perhaps in part explaining cardioprotection in HF that is not mediated directly in cardiomyocytes.</p> },
  year = {2022},
  journal = {Cell Metab},
  volume = {34},
  pages = {1749-1764.e7},
  month = {2022 Nov 01},
  issn = {1932-7420},
  doi = {10.1016/j.cmet.2022.09.008},
  language = {eng},
}