Читать книгу Interventional Cardiology - Группа авторов - Страница 23

Once established, atherosclerosis develops progressively through continuous accumulation of cholesterol‐rich lipids and the accompanying inflammatory response, which can vary considerably among individuals [4]. Early fibroatheroma involves numerous foam cells, extracellular proteoglycans, accumulation of extracellular lipid which progressively distorts the normal architecture of the intima [4]. The extracellular matrix contains collagen, elastin, proteoglycans, and glycosaminoglycans, entrap lipoproteins and promote lipid accumulation which subsequently causes cell necrosis that dominate the central part of the intima, ultimately occupying up to half the volume of the arterial wall and can lead to the formation of flow‐limiting lesions [4,7]. Gradually, the loose fibro cellular tissue is replaced and expanded by collagen‐rich fibrous tissue, with tissues that lie in between a necrotic core and the luminal surface of the plaque (fibrous cap) are fibrous with a high content of type I collagen [72,73]. Macrophages colony stimulating factor (M‐CSF) acts as the main stimulator in this process, next to granulocyte‐macrophage stimulating factor (MG‐CSF) and IL‐2 for lymphocytes [74]. Lymphocytes enter the intima by binding adhesion molecules (VCAM‐1, P‐selectin, ICAM‐1 MCP‐1(CCL2), IL‐8 (CxCL8) [26]. T cells have been proven as a critical driver in the pathogenesis of atherosclerosis, with different T cells subset can serve as a pro‐atherogenic or anti‐atherogenic [75]. CD4+ T helper 1 (TH1) cells and natural killer T cells have pro‐atherogenic roles, on the contrary, regulatory T (Treg) cells have anti‐atherogenic properties [75]. Fernandez et al. [76] showed that the majority of CD4+ T cells in the atherosclerotic plaque are TH1 and TH2, and more TH1 cells are found in plaque compared with peripheral blood. Initially, antigen‐presenting cells (APCs) process oxidised LDL, and present peptides from apolipoprotein B (ApoB) on major histocompatibility complex (MHC) class II molecules to the naïve T cells, which recognise this complex through their specific T cell receptors (TCRs). This process induces T cells to express various transcription factors that favour the differentiation into distinct TH phenotypes and subsequently will differentiate to the complete phenotype of the effector (Teff) or Treg [76]. Even the pro‐atherogenic role for TH1 cells and the anti‐atherogenic role of Treg cells have been well established, the role of the other TH cells subtypes, such as TH2, TH9, TH17, TH22 and follicular helper T (TFH) is still controversial and warrant further investigations [75].