Extra-cardiac BCAA catabolism lowers blood pressure and protects from heart failure.

TitleExtra-cardiac BCAA catabolism lowers blood pressure and protects from heart failure.
Publication TypeJournal Article
Year of Publication2022
AuthorsMurashige, D, Jung, JWoo, Neinast, MD, Levin, MG, Chu, Q, Lambert, JP, Garbincius, JF, Kim, B, Hoshino, A, Marti-Pamies, I, McDaid, KS, Shewale, SV, Flam, E, Yang, S, Roberts, E, Li, L, Morley, MP, Bedi, KC, Hyman, MC, Frankel, DS, Margulies, KB, Assoian, RK, Elrod, JW, Jang, C, Rabinowitz, JD, Arany, Z
JournalCell Metab
Date Published2022 Nov 01
KeywordsAmino Acids, Branched-Chain, Blood Pressure, Energy Metabolism, Heart, Heart Failure, Humans

<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>

Alternate JournalCell Metab
PubMed ID36223763
PubMed Central IDPMC9633425
Grant ListR01 DK114103 / DK / NIDDK NIH HHS / United States
T32 CA257957 / CA / NCI NIH HHS / United States
R01 AG062140 / AG / NIA NIH HHS / United States
T32 HL007843 / HL / NHLBI NIH HHS / United States
R01 HL152446 / HL / NHLBI NIH HHS / United States