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Atherosclerosis: Difference between revisions
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→Lipoprotein entry and modification
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==== ''Lipoprotein entry and modification'' ==== | ==== ''Lipoprotein entry and modification'' ==== | ||
Disruption of the integrity of endothelial barrier due to endothelial dysfunction allows the passage of circulating lipoproteins (low-density lipoprotein, LDL) into the intima. By binding to proteoglycans, LDL | Disruption of the integrity of endothelial barrier due to endothelial dysfunction allows the passage of circulating lipoproteins (low-density lipoprotein, LDL) into the intima. By binding to proteoglycans, LDL particles start to accumulate. This accumulation is a critical process in atherogenesis since LDL may undergo chemical modifications while residing longer in the intima. It is needless to say that an elevated circulating LDL concentration strongly contributes to this accumulating process. Another major risk factor for this process is hypertension since it causes augmented vessel wall stress. Elevated vessel wall stress influences smooth muscle cells to synthesize proteoglycans in the intima, promoting LDL-binding with proteoglycans and therefore contributing to “trapping” of lipoproteins and lipid accumulation within the intima. At this point, macrophages adhere to dysfunctional endothelial cells and transmigrate into the intima. These macrophages are called ‘foam cells’ after they have taken up lipids.<br /> | ||
As mentioned earlier, chemical modification occurs with LDL when chronic accumulation takes place inside the intima. There are several types of chemical modification that may occur. One is called oxidation and it results from the chemical reaction of reactive oxygen species and pro-oxidant enzymes produced by endothelial or smooth muscle cells, or macrophages penetrating the intima. This type of oxidative stress leads to cellular dysfunction and damage in endothelial cells and macrophages. Furthermore chronic hyperglycemia can stimulate glycation of LDL that may ultimately alter LDL into an antigenic and proinflammatory molecule. This explains why diabetes mellitus is a major risk factor for atherosclerosis. The biochemical modification of LDL into a proinflammatory molecule contributes to the inflammation process established by endothelial dysfunction. Furthermore, the oxidized LDL molecule induces tissue damage, which can initiate angiogenesis, forming new vasa vasorum in the plaque. It also induces leukocyte recruitment and foam cell formation in the fatty streak throughout the plaque development.<br /> | As mentioned earlier, chemical modification occurs with LDL when chronic accumulation takes place inside the intima. There are several types of chemical modification that may occur. One is called oxidation and it results from the chemical reaction of reactive oxygen species and pro-oxidant enzymes produced by endothelial or smooth muscle cells, or macrophages penetrating the intima. This type of oxidative stress leads to cellular dysfunction and damage in endothelial cells and macrophages. Furthermore chronic hyperglycemia can stimulate glycation of LDL that may ultimately alter LDL into an antigenic and proinflammatory molecule. This explains why diabetes mellitus is a major risk factor for atherosclerosis. The biochemical modification of LDL into a proinflammatory molecule contributes to the inflammation process established by endothelial dysfunction. Furthermore, the oxidized LDL molecule induces tissue damage, which can initiate angiogenesis, forming new vasa vasorum in the plaque. It also induces leukocyte recruitment and foam cell formation in the fatty streak throughout the plaque development.<br /> | ||