J Lipid Atheroscler.  2019 May;8(1):15-25. 10.12997/jla.2019.8.1.15.

Progression of Multifaceted Immune Cells in Atherosclerotic Development

• Park S
• Lee IK

• KMID: 2447753
• DOI: http://doi.org/10.12997/jla.2019.8.1.15

Abstract

Atherosclerosis is a major cause of morbidity and mortality due to cardiovascular diseases, such as coronary artery disease, stroke, and peripheral vascular disease, that are associated with thrombosis-induced organ infarction. In Westernized countries, the high prevalence of obesity-induced insulin resistance is predicted to be a major factor leading to atherosclerotic vascular disease. Both genetic and environmental factors interfere with immune responses in atherosclerosis development with chronic and non-resolving states. The most known autoimmune disease therapy is cytokine-targeted therapy, which targets tumor necrosis factor-α and interleukin (IL)-17 antagonists. Recently, a clinical trial with the anti-IL-1β antibody (canakinumab) had shown that the anti-inflammatory effects in canakinumab-treated subjects play a critical role in reducing cardiovascular disease prevalence. Recent emerging data have suggested effective therapeutics involving anti-obesity and anti-diabetic agents, as well as statin and anti-platelet drugs, for atherothrombosis prevention. It is well-known that specialized immune differentiation and activation completely depends on metabolic reprogramming mediated by mitochondrial dynamics in distinct immune cells. Therefore, there is a strong mechanistic link between metabolism and immune function mediated by mitochondrial function. In this review, we describe that cellular metabolism in immune cells is strongly interconnected with systemic metabolism in terms of diverse phenotypes and activation.

Keyword

Autoimmunity; Cardiovascular diseases; Hypercholesterolemia; Metabolism; Therapeutics

MeSH Terms

Atherosclerosis
Autoimmune Diseases
Autoimmunity
Cardiovascular Diseases
Coronary Artery Disease
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypercholesterolemia
Infarction
Insulin Resistance
Interleukins
Metabolism
Mitochondrial Dynamics
Mortality
Necrosis
Peripheral Vascular Diseases
Phenotype
Prevalence
Stroke
Vascular Diseases
Interleukins

Figure

• 

  Fig. 1 The stages of atherosclerotic development are as follows. 1) endothelial dysfunction characterized by increased permeability for adhesion molecules, 2) accumulation of lipids within the artery to fatty streaks consisting of monocyte-derived macrophages and T lymphocytes, 3) necrotic core-mediated fibrous cap formation in the lumen of advanced and complex lesions, and 4) unstable fibrous plaque leading to hemorrhage, thrombosis, and occlusions to the artery. oxLDL, oxidized low-density lipoprotein; Ig, immunoglobulin; Ang II, angiotensin II; LDL, low-density lipoprotein; TGF, transforming growth factor; IFN, interferon; MMP, metalloproteinase; Treg, regulatory T cell; Mox, macrophage induced by phospholipids; VSMC, vascular smooth muscle cells.

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