Is Atherosclerosis Equivalent to Cholesterol?

M. Adeva Andany, Department of Nephrology, Hospital Juan Canalejo, Xubias de Arriba, 84, E-15006 La Coruña (Spain) Dear Sir, For the past two decades there has been great controversy over how much the plasma cholesterol should be lowered to prevent cardiovascular disease, without running the risk of potentially serious side effects. Two letters recently published in Nephron [1,2] are an example of this debate. There is no question about the importance of different types of cholesterol in the genesis of atherosclerosis. However, it is necessary to consider other factors that could be of significance and might lead to new strategies in arresting the process of atheromato-sis. In fact, there have been frequent reports of other possible causes of atheromatosis: The virus of the herpes group can induce a latent infection of the cells in the arterial wall, and may set the conditions for the formation of the atherosclerotic plaque [3-8]. Infection by the cytomegalovirus is linked to the sclerotic vascular lesion of chronic graft rejection [9-12]. There are descriptions of Chlamydia pneumoniae as a causative factor of atheromatous plaques [13-15]. The persistent plasmatic elevation of the amino acid homocysteine is a risk factor of vascular disease [ 16] and might be responsible for vascular disease in patients with chronic renal failure [17, 18]. Lowering the plasma levels with folic acid or pyridoxine might be beneficial in these patients. Cocaine is responsible for severe atherosclerosis in different locations, including the kidney [20, 21]. Magnesium depletion [22,23], cyclospo-rin [24-26] and insulin [27] have been cited as agents modulating atherogenesis. Chronic graft rejection is defined as an atherosclerosis-like lesion [28, 29] that accepts, at least in part, an immunologic origin. Similarities in the pathogenesis between atherosclerosis and focal segmental glomerulosclerosis have been recognized [30]. Pre-eclampsia lesions similar to atherosclerosis have been detected in the decidual vessels [31] as well as in the kidney, and focal glomerulosclerosis as seen in primary glomeru-lopathies has been reported [32]. On the other hand, we currently know that the foam cells, which are characteristic of the early phase of the atherogenic process, cannot develop from native cholesterol alone, but rather require the previous modification of the lipoprotein particles to evolve. The intact cholesterol is delivered physiologically to the cells through the LDL receptor. This process is regulated by a negative feedback mechanism that depends on the in-tracellular cholesterol concentration; correspondingly, the cell takes the required amount of cholesterol. When a disequilibrium exists between the oxidant substances and the organic antioxidant defenses, as happens during the generation of free radicals, the LDL particle changes, through an oxida-