Abstract

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.

Highlights

  • Cardiovascular diseases (CVD) currently account for nearly half of the non-communicable diseases and remain the leading cause of death worldwide, with 80% of the deaths occurring in low- and middleincome countries, and coronary artery diseases (CAD) and stroke being the most frequent direct causes of death.[1,2] The underlying cause of CVD is atherosclerosis development, a chronic inflammatory disease that arises from an imbalance in lipid metabolism and a maladaptive immune response.[3]

  • While lipids have been designated as the main dietary contributors to the onset of this inflammatory disease, novel data indicated a potential involvement of some specific amino acids in the process of macrophage foam cell formation, the hallmark feature of early atherogenesis

  • An in-depth investigation (Figure 1) conducted in humans, mice, and cultured macrophages revealed that leucine modified macrophage lipid metabolism with a simultaneous enhancement of mitochondrial respiration, suggesting novel metabolic mechanisms by which leucine inhibits macrophage foam cell formation and atherogenesis, strongly supporting previous reports on the beneficial role of leucine on lipid metabolism and its ability to inhibit tissue lipids accumulation, a key feature of both fatty liver diseases and atherosclerosis development.[50,51,53,54,55,66]

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Summary

Introduction

Cardiovascular diseases (CVD) currently account for nearly half of the non-communicable diseases and remain the leading cause of death worldwide, with 80% of the deaths occurring in low- and middleincome countries, and coronary artery diseases (CAD) and stroke being the most frequent direct causes of death.[1,2] The underlying cause of CVD is atherosclerosis development, a chronic inflammatory disease that arises from an imbalance in lipid metabolism and a maladaptive immune response.[3].

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