Prasad Kailash, Mishra Manish
Department of Physiology (APP), College of Medicine, University of Saskatchewan, Saskatoon, SK S7N 5A2, Canada.
Department of Pharmacology, Dalhousie University, Halifax, NS B3H 4R2, Canada.
Rev Cardiovasc Med. 2022 Jun 9;23(6):212. doi: 10.31083/j.rcm2306212. eCollection 2022 Jun.
Hypercholesterolemia is involved in the development of atherosclerosis and is a risk factor for coronary artery disease, stroke, and peripheral vascular disease. This paper deals with the mechanism of development of hypercholesterolemic atherosclerosis. Hypercholesterolemia increases the formation of numerous atherogenic biomolecules including reactive oxygen species (ROS), proinflammatory cytokines [interleukin (IL)-1, IL-2, IL-6, IL-8, tumor necrosis factor-alpha (TNF- )], expression of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, monocyte chemoattractant protein-1 (MCP-1), granulocyte macrophage-colony stimulating factor (GM-CSF) and numerous growth factors [insulin-like growth factor-1 (IGF-1), platelet-derived growth factor-1 (PDGF-1) and transforming growth factor-beta (TGF- )]. ROS mildly oxidizes low-density lipoprotein-cholesterol (LDL-C) to form minimally modified LDL (MM-LDL) which is further oxidized to form oxidized LDL (OX-LDL). Hypercholesterolemia also activates nuclear factor-kappa-B (NF- B). The above atherogenic biomolecules are involved in the development of atherosclerosis which has been described in detail. Hypercholesterolemia also assists in the development of atherosclerosis through AGE (advanced glycation end-products)-RAGE (receptor for AGE) axis and C-reactive protein (CRP). Hypercholesterolemia is associated with increases in AGE, oxidative stress [AGE/sRAGE (soluble receptor for AGE)] and C-reactive protein, and decreases in the sRAGE, which are known to be implicated in the development of atherosclerosis. In conclusion, hypercholesterolemia induces atherosclerosis through increases in atherogenic biomolecules, AGE-RAGE axis and CRP.
高胆固醇血症与动脉粥样硬化的发生发展有关，是冠状动脉疾病、中风和外周血管疾病的危险因素。本文探讨高胆固醇血症性动脉粥样硬化的发病机制。高胆固醇血症会增加多种致动脉粥样硬化生物分子的形成，包括活性氧（ROS）、促炎细胞因子[白细胞介素（IL）-1、IL-2、IL-6、IL-8、肿瘤坏死因子-α（TNF-α）]、细胞间黏附分子-1（ICAM-1）、血管细胞黏附分子-1（VCAM-1）、E-选择素、单核细胞趋化蛋白-1（MCP-1）、粒细胞巨噬细胞集落刺激因子（GM-CSF）以及多种生长因子[胰岛素样生长因子-1（IGF-1）、血小板衍生生长因子-1（PDGF-1）和转化生长因子-β（TGF-β）]。ROS会使低密度脂蛋白胆固醇（LDL-C）轻度氧化形成轻度修饰的LDL（MM-LDL），MM-LDL会进一步氧化形成氧化LDL（OX-LDL）。高胆固醇血症还会激活核因子-κB（NF-κB）。上述致动脉粥样硬化生物分子参与了动脉粥样硬化的发生发展过程，这已被详细描述。高胆固醇血症还通过晚期糖基化终末产物（AGE）-AGE受体（RAGE）轴和C反应蛋白（CRP）促进动脉粥样硬化的发展。高胆固醇血症与AGE、氧化应激[AGE/可溶性AGE受体（sRAGE）]和C反应蛋白的增加以及sRAGE的减少有关，这些都与动脉粥样硬化的发生发展有关。总之，高胆固醇血症通过增加致动脉粥样硬化生物分子、AGE-RAGE轴和CRP诱导动脉粥样硬化。
