A reappraisal of the mechanisms of hypocholesterolemic action of therapeutic agents.
The most commonly used methods to study the mechanisms of hypocholesterolemic action of therapeutic agents generally determine the turnover of total (exchangeable) cholesterol pools in the body. This approach is based on the view that whatever increases the total load of cholesterol in the body will increase the levels of plasma cholesterol, and vice versa. Despite the importance of this assumption it has never been tested, and there is no evidence to indicate that it is valid under all conditions. This "overload" hypothesis dates from the times before the importance of plasma lipoproteins was recognized and their role in the transport of lipids was well understood. However, it is becoming increasingly clear that the levels of plasma cholesterol are determined more directly by the "transport" of cholesterol into and out of plasma compartment by lipoproteins than by the synthesis, absorption and elimination of cholesterol from the total body pools. Any effects that the latter parameters of cholesterol metabolism have on the levels of plasma cholesterol must be mediated through changes in synthesis and the subsequent metabolism of plasma lipoproteins. In other words, in any equation relating changes in the levels of plasma cholesterol to the changes in synthesis, absorption and elimination of cholesterol from the body pools we must consider the "transport" of cholesterol by lipoproteins and their metabolism.
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000378:metabolism; D001692:Biological Transport / Q000187:drug effects; D002784:Cholesterol / Q000097:blood / Q000378:metabolism; D006801:Humans; D008074:Lipoproteins / Q000378:metabolism; D008954:Models, Biological
D000924:Anticholesteremic Agents; D008074:Lipoproteins; D002784:Cholesterol