ABSTRACT
Already during the early clinical trials with oral synthetic retinoids in the late 1970s, it was noted that a significant proportion of the patients developed hypertriglyceridemia and hypercholesterolemia. Subsequent studies of the plasma lipoproteins showed that there was a shift of cholesterol from the “good” high-density lipoproteins (HDL) to the “bad” low-density lipoproteins (LDL). This was a major concern because such lipid changes are epidemiologically strongly associated with an increased risk of ischemic heart disease (IHD) and stroke, i.e., diseases, which are secondary to atherosclerosis. However, hyperlipidemia is not the only culprit in the pathogenesis of atherosclerosis. Elevated blood pressure, increased blood clotting, smoking, and chronic or acute inflammation causing smooth muscle cell (SMC) proliferation in the blood vessels, have also been incriminated in this process. Recent findings indicate that some of the contributory factors, such as blood clotting and increased SMC proliferation, may in fact be favorably influenced by retinoids. Thus, the question as to whether or not atherosclerosis is promoted during retinoid therapy cannot be answered solely by looking at its effect on blood lipids. The purpose of this chapter is to review the pharmacodynamics of retinoids in hyperlipidemia and atherogenesis, beginning with a short recapitulation of the normal lipid transport in blood.
