Foam, cell damage

It is unlikely that the damaging effects of ox-LDL are relevant only to the walls of blood vessels and there is no reason to suppose they are confined to one disease. The initial histopathologjcal sign of coronary heart disease is the appearance of the fetty streak on the luminal surfece of arteries. Fatty streaks are composed of aggregated macrophages that have taken up ox-LDL via the scavenger receptor. Recently, we have detected such foam cells in the rheumatoid synovium (Section 5.5). 

Fig. 11.1. Atherogenesis is a persistent inflammatory response that occurs in response to conditions that cause endothelial damage (e.g., hypercholesterolemia and oxLDL). After endothelial cells are activated, they elaborate cytokines, chemokines, and other mediators that recruit mononuclear cells (monocytes and T lymphocytes) to extravasate into the vessel wall where they are activated and release additional proinflammatory factors. Macrophages are able to take up oxLDL via scavenger receptors causing them to differentiate into foam cells and form a fatty streak that progresses to an atheroma with a necrotic lipid core and a fibrous cap. Chemokines can lead to weakening of the fibrous cap and eventual plaque rupture leading to thrombosis and occlusion of the involved vessel.

Continued uptake by phagocytes that reside by the endothelial cells of the coronary artery results in their conversion to foam cells, in the invasion of smooth muscle cells, and in eventual narrowing of the lumen of the artery. Evidence suggests that the vitamin E (a-tocopherol) present in LDLs serves to delay the onset of damage to apo B, and give it time to be eventually taken up by the LDL receptor in hepatocytes of the liver. This part of the scenario is shown in the following diagram ... 

Cell damage due to shear forces produced by disintegration of air bubbles Addition of non-ionic detergent may be necessary to prevent foaming, especially in media with a high protein content... 

Free radical damage is considered to be a causative factor in the development of cancer and inflammatory and chronic diseases. Therefore, free radical scavenging molecules (antioxidants) may play a beneficial role in these conditions. With repect to CVD, the oxidation of low-density lipoprotein (LDL) is believed to be a critical process in the development of atherosclerosis (Berliner et al., 1995 Navab et al., 1995). The presence of oxidized LDL in the intima of an artery leads to the production of macrophage-derived foam cells, the main cell type present in fatty streaks that are believed to be the earliest lesion of atherosclerosis (Fuster, 1994). Therefore, the use of antioxidants as dietary supplements to protect against LDL oxidation may reduce both the development and progression of atherosclerosis (Gey, 1995). 

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