Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_3810_Библиотеки_им_академика_М_И_Перельмана

The most widely accepted mechanism of ath­erosclerotic pathogenesis begins when proathero­sclerotic conditions (including disturbed blood ow and hyperlipidemia) lead to endothelial dys­function and stimulate endothelial cells to over­express adhesion molecules including vascular cell adhesion molecule-1 (VCAM-1) on their surfaces. VCAM-1 participates in the recruitment of monocytes and other inammatory cells (e.g., T lymphocytes) to the region [23, 24]. LDL par­ticles become entrapped in the intima by proteo­glycans and are oxidized by oxygen free radicals that are produced by macrophages and other cells [25]. Monocytes enter the intima via diapedesis having been induced into the subendothelial space by chemoattractants, mature into macro­phages and engulf oxidized low-density lipopro­tein (LDL) particles via scavenger receptors. Oxidized LDL is degraded in lysosomes in the macrophage, and excess free cholesterol is trans­ferred to the endoplasmic reticulum where it is esteried into cholesterol esters and packaged into cytoplasmic lipid droplets creating the foam cell [26]. Foam cells produce cytokines and reac­tive oxygen species which further oxidize LDL and recruit modied smooth muscle cells (myo­intimal cells) and T cells into the intima by che­motaxis. Eventually, the pathways to metabolize excess lipoproteins are overwhelmed, and toxic excess free cholesterol builds up leading to cell death. Myointimal cells proliferate and undergo apoptosis, leading to further inammatory sig­naling. As foam cells and myointimal cells undergo apoptosis, necrotic debris and crystal­line cholesterol accumulate in small pools (preatheroma) which coalesce to form larger lipid cores (atheroma) typically leading to plaque expansion from the fourth decade of life.