ArticleJournal of cellular and molecular medicine2018
Branched-chain amino acids promote endothelial dysfunction through increased reactive oxygen species generation and inflammation.
Article in Journal of cellular and molecular medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis that pooled it.
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Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 144 citations in OpenAlex.
- The use of BCAA to decrease delayed-onset muscle soreness after a single bout of exercise: a systematic review and meta-analysis.Amino acids · 2021Pooled it
- Commentary: Unveiling a Metabolic-Lymphatic Axis in the Pathogenesis of Heart Failure With Preserved Ejection Fraction.Cardiology discovery · 2026Article
- Eicosapentaenoic acid ethyl ester, cardiac metabolomic and lipidomic signatures, and cardioprotection in myocardial infarction.European heart journal · 2026Article
- Thromboxane A2-Driven Vascular Hyperreactivity in Cadmium-Induced Hypertension: Role of Oxidative Stress and Therapeutic Implications.Journal of clinical medicine · 2026Article
- Seasonal PMToxics · 2026Article
- Dietary intake and BCAA metabolism regulate pulmonary fibrosis through KDM4A-mediated epigenetic remodeling in male mice.Nature communications · 2026Article
- Metabolic reprogramming in aortic diseases: insights from metabolomics and therapeutic opportunities.Medical review (2021) · 2026Review
- Metabolomic Profiling of Tyrosine Kinase Inhibitor-Induced Endothelial Dysfunction and Cardiovascular Toxicity.Metabolites · 2026Review
- Lifespan-Extending Endogenous Metabolites.Aging cell · 2026Review
- Article
- Endothelial cell metabolism in cardiovascular physiology and disease.Nature reviews. Cardiology · 2025Review
- Altered Expression of Large Amino Acid Transporter (LAT1) and Branched-Chain Metabolic Enzymes in the Type 1 Diabetic Rat Retina.Molecular neurobiology · 2025Article
- Cinnamic acid improves insulin sensitivity in prediabetic mice through branched-chain amino acid metabolic reprogramming.Nutrition & metabolism · 2025Article
- KIF11 variants in familial exudative vitreoretinopathy leading to mTORC1 overactivation and impaired cell cycle progression.Human genomics · 2025Article
- Relationship between sedentary time and cognitive decline in hypertensive patients-mediating role of the weight-adjusted waist circumference index.Scientific reports · 2025Article
- Impacts of aging and fluid shear stress on vascular endothelial metabolism and atherosclerosis development.Journal of biomedical science · 2025Review
- Gut Microbiota and Cardiovascular Diseases: Unraveling the Role of Dysbiosis and Microbial Metabolites.International journal of molecular sciences · 2025Review
- Metabolomics Insights into Salivary Profile in Dogs withBiomolecules · 2025Article
- Dietary branched-chain amino acids intake and coronary artery calcium progression: insights from the coronary artery risk development in young adults (CARDIA) study.European journal of nutrition · 2025Observational
- Metabolomic characterization of unintentional weight loss among community-dwelling older Black and White men and women.Aging cell · 2025Article
37 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Branched-chain amino acids (BCAA: leucine, isoleucine and valine) are essential amino acids implicated in glucose metabolism and maintenance of correct brain function. Elevated BCAA levels can promote an inflammatory response in peripheral blood mononuclear cells. However, there are no studies analysing the direct effects of BCAA on endothelial cells (ECs) and its possible modulation of vascular function. In vitro and ex vivo studies were performed in human ECs and aorta from male C57BL/6J mice, respectively. In ECs, BCAA (6 mmol/L) increased eNOS expression, reactive oxygen species production by mitochondria and NADPH oxidases, peroxynitrite formation and nitrotyrosine expression. Moreover, BCAA induced pro-inflammatory responses through the transcription factor NF-κB that resulted in the release of intracellular adhesion molecule-1 and E-selectin conferring endothelial activation and adhesion capacity to inflammatory cells. Pharmacological inhibition of mTORC1 intracellular signalling pathway decreased BCAA-induced pro-oxidant and pro-inflammatory effects in ECs. In isolated murine aorta, BCAA elicited vasoconstrictor responses, particularly in pre-contracted vessels and after NO synthase blockade, and triggered endothelial dysfunction, effects that were inhibited by different antioxidants, further demonstrating the potential of BCAA to induce oxidative stress with functional impact. In summary, we demonstrate that elevated BCAA levels generate inflammation and oxidative stress in ECs, thereby facilitating inflammatory cells adhesion and endothelial dysfunction. This might contribute to the increased cardiovascular risk observed in patients with elevated BCAA blood levels.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.