小柯机器人

美国宾夕法尼亚大学佩雷尔曼医学院Zoltan Arany团队近期取得重要工作进展，他们研究发现心外支链氨基酸（BCAA）的分解代谢可降低血压并防止心力衰竭。相关论文于2022年10月11日在线发表于《细胞—代谢》杂志上。

研究人员通过体内同位素输注显示，心脏BCAA氧化在HF中实际上是增加而不是减少的。

此外，BCAA氧化的心脏特异性活化不能预防心衰，尽管全身活化可以。降低血浆和心脏BCAAs也不能提供显著的保护，这表明有其他的保护机制。令人惊讶的是，BCAA分解代谢的激活降低了血压（BP），这是一种已知的心脏保护机制。血压降低与一氧化氮无关，反映了血管对肾上腺素能收缩的抵抗。孟德尔随机化研究显示，血浆BCAAs升高预示着人类血压升高。总之，这些数据表明BCAA氧化降低了血管阻力，可能在一定程度上解释了心衰中的心脏保护作用不是由心肌细胞直接介导的。

据介绍，支链氨基酸（BCAA）分解代谢的药理激活是心力衰竭（HF）保护静脉模型。尽管人们普遍认为心脏BCAA氧化过程中会发生致病阻滞，但保护作用如何发生目前仍不清楚。

附：英文原文

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

Author: Danielle Murashige, Jae Woo Jung, Michael D. Neinast, Michael G. Levin, Qingwei Chu, Jonathan P. Lambert, Joanne F. Garbincius, Boa Kim, Atsushi Hoshino, Ingrid Marti-Pamies, Kendra S. McDaid, Swapnil V. Shewale, Emily Flam, Steven Yang, Emilia Roberts, Li Li, Michael P. Morley, Kenneth C. Bedi, Matthew C. Hyman, David S. Frankel, Kenneth B. Margulies, Richard K. Assoian, John W. Elrod, Cholsoon Jang, Joshua D. Rabinowitz, Zoltan Arany

Issue&Volume: 2022-10-11

Abstract: Pharmacologic activation of branched-chain amino acid (BCAA) catabolism is protectivein models of heart failure (HF). How protection occurs remains unclear, although acausative 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 thandecreases, in HF. Moreover, cardiac-specific activation of BCAA oxidation does notprotect from HF even though systemic activation does. Lowering plasma and cardiacBCAAs also fails to confer significant protection, suggesting alternative mechanismsof protection. Surprisingly, activation of BCAA catabolism lowers blood pressure (BP),a known cardioprotective mechanism. BP lowering occurred independently of nitric oxideand reflected vascular resistance to adrenergic constriction. Mendelian randomizationstudies revealed that elevated plasma BCAAs portend higher BP in humans. Together,these data indicate that BCAA oxidation lowers vascular resistance, perhaps in partexplaining cardioprotection in HF that is not mediated directly in cardiomyocytes.

DOI: 10.1016/j.cmet.2022.09.008

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(22)00398-9

Cell Metabolism：《细胞—代谢》，创刊于2005年。隶属于细胞出版社，最新IF：31.373
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