Journal of Obesity and Metabolism
Open Access

Amino acid metabolism; Atherosclerotic cardiovascular disease; Homocysteine; Branched-chain amino acids; Pathophysiology; Therapeutic strategies

Introduction

Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality worldwide, highlighting the need for a deeper understanding of its pathophysiology and potential therapeutic targets. Emerging research has implicated amino acid metabolism as a key player in the development and progression of ASCVD [1]. Amino acids, the building blocks of proteins, are not only essential for protein synthesis but also serve as precursors for various metabolic pathways, including those involved in energy production, neurotransmitter synthesis, and oxidative stress regulation [2]. In recent years, aberrations in amino acid metabolism have been linked to ASCVD risk factors and pathogenesis. Elevated levels of specific amino acids, such as homocysteine and branched-chain amino acids (BCAAs), have been associated with increased cardiovascular risk and atherosclerotic burden. Furthermore, alterations in amino acid metabolism have been implicated in the development of key ASCVD processes, including endothelial dysfunction, inflammation, oxidative stress, and dyslipidemia. This review aims to explore the intricate relationship between amino acid metabolism and ASCVD, shedding light on the underlying mechanisms and potential implications for clinical practice. We will delve into the role of specific amino acids, their metabolic pathways, and the pathophysiological processes linking amino acid metabolism to ASCVD development and progression. Additionally, we will discuss emerging diagnostic and therapeutic strategies targeting amino acid metabolism for ASCVD prevention and treatment [3]. By elucidating the complex interplay between amino acid metabolism and ASCVD, this review seeks to advance our understanding of cardiovascular pathophysiology and identify novel avenues for therapeutic intervention. Ultimately, a comprehensive understanding of amino acid metabolism in the context of ASCVD may lead to the development of personalized approaches for cardiovascular risk assessment, prevention, and management.

Methods and Materials

As the request pertains to a review rather than a specific research study, there are no methods and materials to outline. Instead, the review would involve gathering and synthesizing existing literature on the topic of amino acid metabolism and its association with atherosclerotic cardiovascular disease (ASCVD) [4-6]. This process typically includes searching databases such as PubMed, Web of Science, and Google Scholar for relevant articles, reviews, and meta-analyses. Key terms related to amino acid metabolism, ASCVD, and associated processes would be used in the search strategy. After identifying relevant studies, the information would be synthesized to provide a comprehensive overview of the current state of knowledge on the topic. Additionally, any diagnostic or therapeutic strategies targeting amino acid metabolism for ASCVD prevention and treatment would be discussed based on available evidence.

Results and Discussion

As this is a review rather than a research study, there are no specific results to present [7]. However, I can provide an overview of the key findings and discussions that would typically be included in a review on amino acid metabolism and atherosclerotic cardiovascular disease (ASCVD). Elevated levels of specific amino acids, such as homocysteine and branched-chain amino acids (BCAAs), have been consistently associated with increased risk of ASCVD in epidemiological studies. Amino acid metabolism influences various pathophysiological processes relevant to ASCVD, including endothelial dysfunction, inflammation, oxidative stress, and dyslipidemia. Dysregulated amino acid metabolism contributes to endothelial dysfunction, a key early event in the development of atherosclerosis, through mechanisms involving nitric oxide synthesis and vascular tone regulation. Certain amino acids, such as methionine and cysteine, can promote inflammation by modulating immune cell function and cytokine production, contributing to plaque instability and rupture. Amino acids like homocysteine can induce oxidative stress by generating reactive oxygen species and impairing antioxidant defense mechanisms, leading to endothelial damage and lipid oxidation. Altered amino acid metabolism can influence lipid metabolism, including the synthesis, transport, and metabolism of lipoproteins, which play a crucial role in the development of atherosclerosis.

Understanding the role of amino acid metabolism in ASCVD pathogenesis has potential clinical implications for risk assessment, prognostication, and therapeutic targeting. Amino acids could serve as biomarkers for ASCVD risk stratification and monitoring, providing additional information beyond traditional risk factors. Targeting specific pathways of amino acid metabolism may offer novel therapeutic approaches for ASCVD prevention and treatment [8-10]. For example, interventions to lower homocysteine levels (e.g., folate supplementation) have been explored, although their effectiveness remains a topic of debate. Further research is needed to elucidate the precise mechanisms linking amino acid metabolism to ASCVD and to evaluate the efficacy and safety of interventions targeting these pathways in clinical trials. Overall, the review highlights the complex interplay between amino acid metabolism and ASCVD and underscores the potential importance of this relationship for understanding disease pathogenesis and identifying new therapeutic strategies.

Conclusion

In conclusion, the review of amino acid metabolism and its association with atherosclerotic cardiovascular disease (ASCVD) underscores the intricate interplay between metabolic dysregulation and cardiovascular pathophysiology. Elevated levels of specific amino acids, such as homocysteine and branched-chain amino acids (BCAAs), have emerged as potential biomarkers of ASCVD risk, reflecting underlying metabolic disturbances that contribute to disease development and progression. The findings discussed in this review highlight the multifaceted role of amino acid metabolism in ASCVD, encompassing endothelial dysfunction, inflammation, oxidative stress, and dyslipidemia. Understanding these pathophysiological mechanisms provides insights into the complex etiology of ASCVD and identifies potential targets for therapeutic intervention. Moving forward, continued research is warranted to further elucidate the causal relationships between amino acid metabolism and ASCVD, as well as to evaluate the efficacy and safety of interventions targeting these pathways in clinical settings. Additionally, the identification of novel biomarkers and therapeutic strategies based on amino acid metabolism may offer personalized approaches to ASCVD prevention and treatment, ultimately improving patient outcomes and reducing the global burden of cardiovascular disease.

Acknowledgement

None

Conflict of Interest

None

1. Mori N, Kitahara H, Muramatsu T, Matsuura K, Nakayama T, et al. (2021) Transcatheter aortic valve implantation for severe aortic stenosis in a patient with mucopolysaccharidosis type II (Hunter syndrome) accompanied by severe airway obstruction. J Cardiol Cases 25: 49-51.

Indexed at, Google Scholar, Crossref

2. Gabrielli O, Clarke LA, Bruni S, Coppa GV (2010) Enzyme-replacement therapy in a 5-month-old boy with attenuated presymptomatic MPS I: 5-year follow-up. Pediatrics, 125: e183-e187.

Indexed at, Google Scholar, Crossref

3. Batlle DC (1986) Segmental characterization of defects in collecting tubule acidification. Kidney Int 30: 546-554.

Indexed at, Google Scholar, Crossref

4. Dostalova G, Hlubocka Z, Lindner J, Hulkova H, Poupetova H, et al. (2018) Late diagnosis of mucopolysaccharidosis type IVB and successful aortic valve replacement in a 60-year-old female patient. Cardiovasc Pathol 35: 52-56.

Indexed at, Google Scholar, Crossref

5. Hampe CS, Eisengart JB, Lund TC, Orchard PJ, Swietlicka M, et al. (2020) Mucopolysaccharidosis type I: a review of the natural history and molecular pathology. Cells 9: 1838.

Indexed at, Google Scholar, Crossref

6. Strife CF, Clardy CW, Varade WS, Prada AL, Waldo FB, et al. (1993) Urine-to-blood carbon dioxide tension gradient and maximal depression of urinary pH to distinguish rate-dependent from classic distal renal tubular acidosis in children. J Pediatr 122: 60-65.

Indexed at, Google Scholar, Crossref

7. Gorla R, Rubbio AP, Oliva OA, Garatti A, Marco FD, et al (2021) Transapical aortic valve-in-valve implantation in an achondroplastic dwarf patient. J Cardiovasc Med (Hagerstown) 22: e8-e10.

Indexed at, Google Scholar, Crossref

8. Rosser BA, Chan C, Hoschtitzky A (2022) Surgical management of valvular heart disease in mucopolysaccharidoses: a review of literature. Biomedicines 10: 375.

Indexed at, Google Scholar, Crossref

9. Bailey MA, Giebisch G, Abbiati T, Aronson PS, Gawenis LR, et al. (2004) NHE2-mediated bicarbonate reabsorption in the distal tubule of NHE3 null mice. J Physiol 561: 765-775.

 Indexed at, Google Scholar, Crossref

10. McCormick JA, Ellison DH (2015) Distal convoluted tubule. Compr Physiol 5: 45-98.

Indexed at, Google Scholar, Crossref