The formation and causes of Atherosclerosis have several theories as following:
1. Lipid infiltration:
Atherosclerosis is related to lipid metabolism disorders, the nature of the arterial wall from the plasma lipid response to the invasion. Atherosclerosis is the main pathological changes in artery wall slab-like plaques appeared, while the cholesterol and cholesterol ester is the main component of atherosclerotic plaque. Although the artery wall can also cholesterol and other lipid synthesis, but in recent years on the artery wall and endothelial cell physiology and pathology, as well as atherosclerotic lesions and immune histochemical results of chemical examination confirmed the lipid plaque mainly from the plasma quality. Plasma cholesterol, triglycerides and phospholipids are combined with the apolipoprotein and lipoprotein dissolved operation. LDL cholesterol and cholesterol ester containing up to, VLDL triglyceride containing a maximum of, HDL protein containing most of the lipid increased plasma LDL and VLDL that is, or intima surface of the role of lipoprotein lipase into the form of pieces invasive way from the artery wall:
1) pinocytotic endothelial cells directly;
2) gap through the endothelial cells;
3) via the LDL receptor in endothelial cells;
4) increased permeability through the damaged endothelial cells;
5) through due to lack of endothelial cells directly exposed to the endometrial tissue blood flow.
After lipoprotein into the membrane, the accumulation in the smooth muscle cells, collagen and elastic fibers, causing smooth muscle cell proliferation, smooth muscle cells and monocytes from the blood of a large number of lipid phagocytosis become foam cells; lipoprotein degradation and release again of cholesterol, cholesterol esters, triglycerides and other lipids, LDL with arterial wall proteoglycans precipitate insoluble combination, can stimulate the proliferation of fibrous tissue. All of these together to form plaque.
HDL in lipoprotein can transport cholesterol to the liver and break down, inhibition of LDL uptake and inhibition of proliferation of smooth muscle cells, which are considered to have anti-atherogenic role. After lipid oxidation cause lipid peroxidation, and cytotoxicity, membrane damage, and cause atherosclerosis.
2. Thrombosis and platelet aggregation:
The former believe that the beginning of atherosclerosis in hyper local clotting mechanism, arterial intimal surface of thrombosis, hyperplasia after the thrombosis was covered by endothelial cells and into the arterial wall, thrombosis of the platelet and leukocyte disintegration and release of lipids and other active substances, the gradual formation of atherosclerotic plaque. The latter believe that the beginning of atherosclerosis in the arterial intimal damage, platelet-activating factor (PAF) increase in adhesion followed by platelet aggregation in the area, followed by fibrin deposition occur, forming microthrombus. Platelet aggregation activity after the release of some material. Which thromboxane A2 (thromboxane A2, TXA2) to fight against the vessel wall synthesis of prostacyclin (prostacycline, PGI2) have to make the depolymerization of platelet and blood vessels to expand the role of, and to promote further platelet aggregation and vasoconstriction; platelet-derived growth factor (platelet derived growth factor) can stimulate smooth muscle cell hyperplasia, and endometrial wavering contraction; 5 - HT and fibroblast growth factor (fibroblast growth factor) can stimulate fibroblasts, smooth muscle cells and endothelial cells, epinephrine and ADP can promote further platelet aggregation: platelet factor Ⅷ make further adhesion; platelet factor 4 (platelet factor4) vasoconstriction can; plasminogen activator inhibitor (PAI) so that the dissolution was inhibited thrombosis . Of these substances so that further damage endothelial cells, resulting in LDL, fibrinogen into the intima and subintimal; so that monocyte accumulation in the intima, foam cells develop into; so that smooth muscle cell proliferation into the intima, lipid phagocytosis; and endothelial cell proliferation is causes of atherosclerosis.
3. The injury response:
It is believed that the formation of plaque on artery intimal response to injury. Intima intimal injury can be manifested in disorders such as endometrial infiltration had increased, the surface of the formation of thrombus easy. Can also be reflected in the integrity of endometrial damage. Long-term hyperlipidemia, due to increased blood pressure, arterial branches and to the specific point of view, such as vascular stenosis causes local hemodynamic changes resulting from turbulence, shear stress, as well as diabetes, smoking, bacteria, viruses, toxins, immune factors and vasoactive substances such as catecholamines, 5 - HT, histamine, bradykinin, endothelin, angiotensin, such as the role of long-term repeated; are enough to cause damage or functional changes in endometrium, in favor of lipid deposition and platelet adhesion and aggregation, and cause atherosclerosis.
4. Single cell breeding:
It is believed that atherosclerotic lesions are each derived from a single smooth muscle cell proliferation after the cells are generated by the ancestor of many cells. In a number of factors such as platelet-derived growth factor, endothelial cell-derived growth factor, monocyte derived growth factor, LDL, and possibly the role of virus proliferation and phagocytosis under the lipid, which is similar to benign tumors, and the formation of atherosclerosis . Although the adoption of glucose -6 - phosphate dehydrogenase (G6PD) isoenzyme determination and found that the vast majority of fibrous plaque lesions in the artery wall contains only a G6PD isozyme, shows characteristics of fibrous plaques monoclonal. But also that the disease phenotype of the single-enzyme does not necessarily mean that the origin of this lesion is clonal, and may also contain the same isozyme from the number of cells, however, as a result of repeated cell death and growth, so that results shows that single-enzyme phenotype. In fact within the atherosclerotic plaque smooth muscle cells were cultured, these cells have not yet shown will be the same as unlimited proliferation of tumor.
5. Others: The other mechanism of the pathogenesis are still nervous, endocrine changes in artery wall polysaccharide matrix acidic protein quality and quantity changes (increase in dermatan sulfate, and chondroitin sulfate A and C reduction), arterial wall the reduction of such activity. These circumstances can affect vasomotor, lipid metabolism, vessel wall metabolism will cause atherosclerosis.