Pathogenesis of Atherosclerosis Research Progress _2317

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Pathogenesis of Atherosclerosis Research Progress
 
 
Keywords: Progress   Keywords: atherosclerosis; pathogenesis; Research   atherosclerosis by lipid, carbohydrate, blood components stove -like deposition, connective tissue and calcium deposits caused by, associated with changes in medial joint disease, it is the most serious human health hazard of cardiovascular disease. People generally believe that atherosclerosis is a multi-factor multi-channel interaction. In recent years, the pathogenesis of increased, and made important progress in many areas, the most important thing is found in the following aspects in the pathogenesis of atherosclerosis in the role.    1 The role of endothelial dysfunction    studies have shown that atherosclerosis are associated with various stages of endothelial dysfunction, and many coronary events the occurrence of coronary vascular endothelial dysfunction are closely related. Endothelial dysfunction of atherosclerosis is an early event, caused by risk factors for atherosclerosis can cause coronary vascular endothelial dysfunction. Results demonstrated that risk factors can be detected in the formation of atherosclerotic coronary artery existed prior to endothelial dysfunction. On the other hand, controlling risk factors can improve endothelial function. Endothelial dysfunction can be caused by abnormal blood vessel contraction, tension increased, platelet adhesion, aggregation, thrombosis and arterial vascular smooth muscle cells in the membrane (VSMC) proliferation, thus endothelial dysfunction on the incidence of coronary artery disease, initiating the development and facilitating role. Recent studies show that vascular endothelial cells are the body's largest and very active endocrine function, metabolism of paracrine and autocrine organ, can be dozens of production and secretion of bioactive substances, the angiotensin Ⅱ (Ang Ⅱ) not only lead to high blood pressure, also involved in atherosclerosis and thrombosis mechanisms. In addition, Ang Ⅱ itself through a variety of different mechanisms leading to thrombosis, such as generating oxidized low-density lipoprotein 2 (OX2 low-density lipoprotein), the adhesion molecule angiogenesis, inflammatory proteins. These can promote the formation of atherosclerosis and may promote atherosclerotic plaque rupture [1].    2 apoptosis    apoptosis in the arterial wall hardening process plays an important role. Apoptotic cells are often distributed in the cell population, mainly by macrophages and smooth muscle cells. Atherosclerosis in general damage, not all samples have the corresponding apoptosis, but almost all caused by atherosclerotic stenosis were apoptosis, which may be related to intimal hyperplasia. Recent studies show that cardiovascular apoptosis in the existence of a potential oxidative mechanisms. In addition, cardiovascular smooth muscle cell apoptosis, at least to some extent, is due to oxidant hydrogen peroxide (H2O2) caused the damage. Also on L2 arginine / nitric oxide (NO) synthase have been studied in sufficient quantities that arginine can induce intimal injury L2 in macrophage apoptosis, which is due to cell metabolism's sake, NO, It is through a cyclic guanosine monophosphate (cGMP)-independent pathway to achieve, that further study of NO synthase for the treatment of atherosclerosis pathway provides a theoretical basis [2].    3 macrophage colony-stimulating factor role    macrophage colony-stimulating factor can promote monocyte accumulation and foam cell formation [3] regulate intimal smooth muscle cells (SMC) function. The early formation of atherosclerosis, mononuclear cell aggregation tendency in the area of ​​intimal lesions, in vascular endothelial cells, SMC and mononuclear cells (MC) produced by macrophage colony stimulating factor and monocytic cell wall endocardium clearance, macrophage colony-stimulating factor and MC surface macrophage colony-stimulating factor receptor binding, activation of MC, the expression of proliferating cell nuclear antigen (PC2NA) capacity enhancement [4], to promote their proliferation and differentiation to macrophages. Macrophages to produce proteases, fatty acid, free radicals, reactive oxygen species and other cell toxin-mediated inflammatory response, while low-density lipoprotein oxidation into oxidized low density lipoprotein (OX2 low-density lipoprotein) and rely on their scavenger OX2 intake of a large number of low density lipoprotein receptor, the formation of atherosclerotic foam cells characteristic 2. Mozes [5] and so confirm that macrophage colony-stimulating factor allows single-macrophage accumulation in the vascular wall and cause smooth muscle cell proliferation and migration, and promote the development of atherosclerosis.    4 The role of osteoprotegerin  Senile Osteoporosis is often accompanied by atherosclerosis and vascular calcification. Found that atherosclerotic plaques and calcification damage zone with) a variety of bone matrix proteins and osteoblast markers (such as type Ⅰ antigen, osteocalcin, osteonectin, osteopontin, matrix carboxyglutamic acid protein ν2 , bone morphogenetic protein 2 and hydroxyl apatite collectively referred to as osteoprotegerin), and recognizing the vessel wall calcification and bone mineralization may be some intrinsic link [6 ~ 8]. Osteoprotegerin (or OPG) deficiency, the occurrence of osteoporosis and vascular wall calcification, and atherosclerotic vessel wall to provide favorable conditions.    5 iron to increase the role of    lipid oxidation of low density lipoprotein and plaque formation of the vascular system leading to the key. Oxidized low density lipoprotein caused a large number of macrophages in the lipid endocytosis, resulting in foam cells in the formation of plaque accumulation under the vascular endothelium, causing vascular injury [9]. In 1981, it was suggested that the Organization study found that in the early atherosclerotic lesions, a large number of iron deposition in the lysosomes of foam cells at [10]. Atherosclerosis in human aorta specimens were found in macrophages and smooth muscle cells were increased iron deposition inside and outside, while iron and ceroid deposition site (complexes of lipid and protein oxidation end products) consistent in the the lesion is also seen large amounts of iron protein. Iron deposition and aortic atherosclerosis was positively correlated with the severity. Animal experiments also show that high iron diet increased lipid peroxidation of low density lipoprotein, and low iron diet on the contrary. Iron chelating agents can protect tissue damage and the artery atherosclerosis.    6 insulin resistance    blood flow caused by insulin resistance not only to reduce peripheral vascular resistance increased, but also can cause dyslipidemia, hypertension and atherosclerosis sclerosis, insulin resistance and atherosclerosis may be in the polygenic basis of the joint action of various environmental factors was gradually formed. Insulin resistance can lead to lipid metabolism, in particular small dense LDL particles increased 2C, TG HDL2C rise and fall, insulin, lipids with induced plasminogen activator inhibitor (PAI) 21 increased the expression of the blood was hypercoagulable state, insulin resistance also promotes the expression of adhesion molecules, arterial wall endothelial cells promote plaque formation. Insulin resistance may cause hypertension, endothelial cell dysfunction, insulin resistance with obesity has a number of factors cause atherosclerosis, insulin resistance is also often accompanied by hyperuricemia, serum uric acid can enhance platelet aggregation and adhesion. In insulin resistance, cytokines, adipokines, growth factors and adhesion molecules increased significantly, while vascular endothelial asymmetric dimethylarginine (ADMA) increased, ADMA inhibition of NO synthase, NO generation decreased vasodilation weakened, endothelial cell dysfunction, indicating that insulin resistance and atherosclerosis has the same molecular mechanisms and reinforce each other [11].    7 The role of Chlamydia pneumoniae    after Chlamydia pneumoniae invasion of the body mainly through two mechanisms involved in atherosclerosis: (1 ) Chlamydia pneumoniae antigens, such as LPS, heat shock protein 60 and cysteine-rich outer membrane protein (MOMP) and so induce antibodies, and the arterial wall immune attack target cells, causing antibody dependent cell poison. (2) single-core 2 as a carrier of macrophages, the alveolar parts of Chlamydia pneumoniae by a stranger, to migrate to the arterial wall, and endothelial cells, vascular smooth muscle cells and macrophages in chronic persistent infection, induced the expression of cytokines and adhesion molecules , leading to endothelial cell damage, foam cell formation, vascular smooth muscle cell proliferation, and matrix collagen persistent changes. In the whole population, Chlamydia pneumoniae infection is extremely common, infection incidence of atherosclerosis to some extent depends on the individual genetic susceptibility, is also determined by pathogenic factors, host specificity and non-specific cellular and humoral immunological activity; histocompatibility complex polymorphism from the gene pool on the invasion created a reaction to the antigen and susceptibility to different studies have shown that C. pneumoniae infection, the incidence of atherosclerosis and leukocyte antigens state is closely related, but the exact mechanism needs further study [12]. 

     References    1 ZHANG Jun-hua 1, vascular endothelial dysfunction and coronary artery disease, a Chinese Journal of cardiovascular and cerebrovascular disease aged, 2002, 4 (1): 3    2 Towbin JA1The role of cytoskeletail proteins in cardiomy OPthies1opinion Cell Biol, 1998, 10 (1): 131    3 Qiao JH, Tripathi J, Mishra NK et al1Role of macrphage colonystimulating factor in herosclerosis: studies of osteopetrotic etroticmice1Am J Pathol, 1997, 150: 1687    4 Wang J, Wang S, Lu Y et al1GM2CSF and M2CSF expression is as2sociaeed with macrophage roliferation in progressing and regressingrabbit atherolmatous lesions1Exp Mol athol, 1994, 61: 109    5 Mozes G, Mohacsi F, Glovizki P et al1Adenovirus2Mediated genetransfer of macrophage colony lating factor to the arterial wallin vivo1Arteroscler Thromb Vasc Biol, 1998, 18: 1157    6 Simonnet WS, Lacey DL, Dunstan CR et al1Osteoprotegerin: a nov2el secreted protein involved in the regulation of bone density1 Cell, 1997, 89: 309    7 Bucay N, Sarosi I, Dunstan CR et al1osteoprotegerin2deficient micedevelop early onset osteoporosis and arterial calcification1GenesDev, 1998, 12: 12608 Min H, Morony S, Sarosi I et l1Osteoprotegerin reverses osteo2porosis by inhibiting endosteal osteoclasts and prevents vascular cal2cification by blocking a process resembling osteclastogensis1J ExpMED, 2000, 192: 463    9 Hovoet P, Collen D1Oxidation of low density lipoproteins in thepathogenesis therosclerosis1Atherosclerosis , 1998, 137 (Suppl): 33    10 Vlad M, caseanu E, Uza G et al1Concentration of copper, zinc, chromium, iron and nickel in the abdominal aorta of patients de2ceased with coronary heart disease1J Trace Elem Electrolytes HealthDis, 1994, 8: 111    11 Luo Min 1, insulin resistance and atherosclerosis Journal of Internal Medicine 1, 2002, 41 (9): 636    12 Han Bin Cui, Chang-Cong Cui 1 Chlamydia pneumoniae infection on the pathogenesis of atherosclerosis research progress in Chinese Internal Medicine 1,You are not allowed to view links. Register or Login, 2002, 41 (4): 281