Molecular regulation of cholesterol metabolism: HDL-based intervention through drugs and diet.

ABSTRACT

The overloading of cholesterol in the arteries remains the principal cause of cardiovascular diseases. Since available anti-cholesterolemic drugs are not completely effective and have several severe adverse effects, the aim of this review is to analyze current research focused on the emerging, innovative therapeutic strategies based on both pharmacological and nutritional interventions to control cholesterol metabolism. Pharmacological interventions mainly involve the use of molecules capable of interfering with high-density lipoprotien (HDL) metabolism and the reverse cholesterol transport (RCT) through genetic control of apolipoprotein A-I (ApoA-I), agonism at liver X-receptor a (LXRa), or inhibition of cholesteryl ester transport protein (CETP), scavenger receptor BI(SR-BI), and ecto F0F1ATPase/synthase. Nutritional interventions are based on the use of fibres, phytosterols, and probiotics acting through interference with absorption and re-absorption of cholesterol by enterocyte and hepatocyte specific transporters, thus influencing RCT final step. The search for new drugs is still at the very beginning and new molecules are not yet ready to enter clinical use. However, several promising findings coming from innovative biotechnological research are expected shortly to produce probiotics, fibres, and phytosterols to be used as therapeutic tools. Among the most important advantages of natural products in respect to traditional drugs are the lack of severe adverse effects and their low cost.