Branched-chain amino acids and atherosclerosis: friends or foes?

Grajeda‐Iglesias, Claudia; Rom, Oren; Aviram, Michael

doi:10.1097/mol.0000000000000494

Cited by 11 publications

(7 citation statements)

References 21 publications

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“…One particular study observed increased levels of circulating BCAAs in CVD, diabetes, IR, obesity, and healthy individuals, independently of body mass index (97). Metabolic status is the key element that determines whether increased levels of a particular BCAA has a positive or negative influence on CVD risk (97,98). In this regard, it is known that some stimuli can impact tissues involved in BCAA clearance, such as brown adipose tissue (BAT), a well-known thermogenic (and BCAA catabolic) organ.…”

Section: The Role Of Bcaas In Atherosclerosismentioning

confidence: 99%

“…On the other hand, a decrease in cellular triglycerides results from inhibition of the enzyme, diacylglycerol acyltransferase-1, which catalyzes the synthesis of triglycerides in macrophages. One particular study observed increased levels of circulating BCAAs in CVD, diabetes, IR, obesity, and healthy individuals, independently of body mass index (97). Metabolic status is the key element that determines whether increased levels of a particular BCAA has a positive or negative influence on CVD risk (97,98).…”

Section: The Role Of Bcaas In Atherosclerosismentioning

confidence: 99%

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Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes

et al. 2020

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Cardiovascular disease is the leading global health concern and responsible for more deaths worldwide than any other type of disorder. Atherosclerosis is a chronic inflammatory disease in the arterial wall, which underpins several types of cardiovascular disease. It has emerged that a strong relationship exists between alterations in amino acid (AA) metabolism and the development of atherosclerosis. Recent studies have reported positive correlations between levels of branched-chain amino acids (BCAAs) such as leucine, valine, and isoleucine in plasma and the occurrence of metabolic disturbances. Elevated serum levels of BCAAs indicate a high cardiometabolic risk. Thus, BCAAs may also impact atherosclerosis prevention and offer a novel therapeutic strategy for specific individuals at risk of coronary events. The metabolism of AAs, such as L-arginine, homoarginine, and L-tryptophan, is recognized as a critical regulator of vascular homeostasis. Dietary intake of homoarginine, taurine, and glycine can improve atherosclerosis by endothelium remodeling. Available data also suggest that the regulation of AA metabolism by indoleamine 2,3-dioxygenase (IDO) and arginases 1 and 2 are mediated through various immunological signals and that immunosuppressive AA metabolizing enzymes are promising therapeutic targets against atherosclerosis. Further clinical studies and basic studies that make use of animal models are required. Here we review recent data examining links between AA metabolism and the development of atherosclerosis.

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Section: The Role Of Bcaas In Atherosclerosismentioning

confidence: 99%

Section: The Role Of Bcaas In Atherosclerosismentioning

confidence: 99%

Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes

et al. 2020

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“…Therefore, whether BCAA are the cause per se, an epiphenomenon of, or indicators of cardio-metabolic disturbance remains the paramount question. 47 To investigate this further, interventional studies including supplementation with BCAA have been carried out in cells, in animal models, and in human populations. While BCAA-supplemented blood mononuclear cells showed increased production of reactive oxygen species (ROS) via both NADPH oxidase and the whole mitochondria, stimulating the activation of the redox-sensitive transcription factor NF-κB, which resulted in the release of pro-inflammatory molecules, 48 BCAA supplementation reduced the expression of interleukin (IL)-6, IL-1β, IL-18, and tumor necrosis factor-α (TNFα) mRNA in the liver, as well as the amount of hepatic triglycerides accumulation, together with inhibition of macrophage infiltration, in the white adipose tissue of obese mice.…”

Section: Branched-chain Amino Acid As Biomarkers For Cvd Riskmentioning

confidence: 99%

Specific Amino Acids Affect Cardiovascular Diseases and Atherogenesis via Protection against Macrophage Foam Cell Formation: Review Article

Grajeda‐Iglesias¹,

Aviram²

2018

Rambam Maimonides Med J

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The strong relationship between cardiovascular diseases (CVD), atherosclerosis, and endogenous or exogenous lipids has been recognized for decades, underestimating the contribution of other dietary components, such as amino acids, to the initiation of the underlying inflammatory disease. Recently, specific amino acids have been associated with incident cardiovascular disorders, suggesting their significant role in the pathogenesis of CVD. Special attention has been paid to the group of branched-chain amino acids (BCAA), leucine, isoleucine, and valine, since their plasma values are frequently found in high concentrations in individuals with CVD risk. Nevertheless, dietary BCAA, leucine in particular, have been associated with improved indicators of atherosclerosis. Therefore, their potential role in the process of atherogenesis and concomitant CVD development remains unclear. Macrophages play pivotal roles in the development of atherosclerosis. They can accumulate high amounts of circulating lipids, through a process known as macrophage foam cell formation, and initiate the atherogenesis process. We have recently screened for anti- or pro-atherogenic amino acids in the macrophage model system. Our study showed that glycine, cysteine, alanine, leucine, glutamate, and glutamine significantly affected macrophage atherogenicity mainly through modulation of the cellular triglyceride metabolism. The anti-atherogenic properties of glycine and leucine, and the pro-atherogenic effects of glutamine, were also confirmed in vivo. Further investigation is warranted to define the role of these amino acids in atherosclerosis and CVD, which may serve as a basis for the development of anti-atherogenic nutritional and therapeutic approaches.

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“…Atherosclerosis, the underlying cause of most CVDs, is a chronic disease of the arteries arising from imbalanced lipid metabolism, a maladaptive immune response, and dysregulated redox homeostasis (Griendling et al, 2016;Moore et al, 2013). While the association between altered lipid metabolism and CVDs is well established, recent evidence indicates that dysregulated metabolism of specific amino acids plays an important role in the pathogenesis of atherosclerosis (Grajeda-Iglesias et al, 2018;Nitz et al, 2019;Rom et al, 2018;Zaric et al, 2020). Among all amino acids, lower circulating glycine is emerging as a common denominator in CVDs and related metabolic comorbidities (Rom et al, 2018), including coronary heart disease (Wittemans et al, 2019), myocardial infarction (Ding et al, 2015), obesity (Newgard et al, 2009), type 2 diabetes (T2D) (Guasch-Ferré et al, 2016), metabolic syndrome (Li et al, 2018), and non-alcoholic fatty liver disease (NAFLD) (Gaggini et al, 2018.…”

Section: Introductionmentioning

confidence: 99%

Dysregulated oxalate metabolism is a driver and therapeutic target in atherosclerosis

Wang¹,

Zhao²,

Shukha³

et al. 2021

Cell Reports

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Branched-chain amino acids and atherosclerosis: friends or foes?

Cited by 11 publications

References 21 publications

Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes

Atherosclerosis Linked to Aberrant Amino Acid Metabolism and Immunosuppressive Amino Acid Catabolizing Enzymes

Specific Amino Acids Affect Cardiovascular Diseases and Atherogenesis via Protection against Macrophage Foam Cell Formation: Review Article

Dysregulated oxalate metabolism is a driver and therapeutic target in atherosclerosis

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