Two Treatments for Atherosclerosis Are Based on SREBPRegulated Cellular Cholesterol Metabolism

The complex pathogenesis of atherosclerosis, which we have only briefly sketched here, presents a daunting challenge to modern molecular medicine. However, as our understanding of the cell biology underlying this complexity has advanced, many opportunities for intervening in the disease process by modulating cellular pathways have arisen. We conclude this chapter by describing two examples of such interventions affecting cellular lipid metabolism.

Because the risk for atherosclerotic disease is directly proportional to the plasma levels of LDL cholesterol and inversely proportional to those of HDL cholesterol, a major public health goal has been to lower LDL and raise HDL cholesterol levels. The most successful drug interventions to date have been aimed at reducing plasma LDL. The steady-state levels of plasma LDL are determined by the relative rates of LDL formation and LDL removal or clearance. LDL receptors, especially those expressed in the liver, play a major role in clearing LDL from the plasma. The liver is key in cholesterol regulation not only because it is the site of about 70 percent of the body's LDL receptors, but also because it is the site where unesterified cholesterol and its bile acid

Liver cell

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