Aberrant branched-chain amino acid catabolism in cardiovascular diseases

Abstract

Globally, cardiovascular diseases are the leading cause of death. Research has focused on the metabolism of carbohydrates, fatty acids, and amino acids to improve the prognosis of cardiovascular diseases. There are three types of branched-chain amino acids (BCAAs; valine, leucine, and isoleucine) required for protein homeostasis, energy balance, and signaling pathways. Increasing evidence has implicated BCAAs in the pathogenesis of multiple cardiovascular diseases. This review summarizes the biological origin, signal transduction pathways and function of BCAAs as well as their significance in cardiovascular diseases, including myocardial hypertrophy, heart failure, coronary artery disease, diabetic cardiomyopathy, dilated cardiomyopathy, arrhythmia and hypertension.

Toxicometabolomics-Based Cardiotoxicity Evaluation of Thiazolidinedione Exposure in Human-Derived Cardiomyocytes.

“…In addition, modulation of amino acids has been associated with cardiac remodelling (Geng et al, 2020;Karwi & Lopaschuk, 2023). The high levels of BCAAs found in our toxicometabolomics analysis have been reported to activate the mammalian target of the rapamycin (mTOR) signalling pathway, a crucial hypertrophic signalling pathway implicated in HF patho-mechanisms (Xiong et al, 2022). L-tyrosine is another amino acid that has been hooked with cardiac hypertrophy, as its involvement was supported by a recent study performed to investigate the pathophysiological process of doxorubicin-induced cardiotoxicity (Geng et al, 2020).…”

“…Re ecting on the amino acid pro le, modulation in branched-chain amino acids (BCAAs) represented with high levels of L-leucine, L-isoleucine and valine was noted in our analysis. Growing clinical and preclinical evidence has proposed elevated levels of BCAAs as a predictor of a wide range of cardiovascular diseases, including HF (Xiong et al, 2022). These ndings surprisingly contradict the crucial roles that BCAAs play in cardiac energy metabolism.…”

Toxicometabolomics-based cardiotoxicity evaluation of Thiazolidinedione exposure in human-derived cardiomyocytes

“…In addition, modulation of amino acids has been associated with cardiac remodelling (Geng et al, 2020 ; Karwi & Lopaschuk, 2023 ). The high levels of BCAAs found in our toxicometabolomics analysis have been reported to activate the mammalian target of the rapamycin (mTOR) signalling pathway, a crucial hypertrophic signalling pathway implicated in HF patho-mechanisms (Xiong et al, 2022 ). L-tyrosine is another amino acid that has been hooked with cardiac hypertrophy, as its involvement was supported by a recent study performed to investigate the pathophysiological process of doxorubicin-induced cardiotoxicity (Geng et al, 2020 ).…”

“…Reflecting on the amino acid profile, modulation in branched-chain amino acids (BCAAs) represented with high levels of L-leucine, L-isoleucine and valine was noted in our analysis. Growing clinical and preclinical evidence has proposed elevated levels of BCAAs as a predictor of a wide range of cardiovascular diseases, including HF (Xiong et al, 2022 ). These findings surprisingly contradict the crucial roles that BCAAs play in cardiac energy metabolism.…”

Overview of chromatographic and electrophoretic methods for the determination of branched‐chain amino acids

“…BCAAs also have an impact on neurotransmission and glucose metabolism [3]. The mammalian/mechanistic target of rapamycin complex 1 signaling is one of the metabolic reactions regulated by Leu [4]. Activating the mammalian target of the rapamycin signaling pathway may contribute to insulin resistance.…”