Effects of Statin and Ezetimibe Association on Kinetics of Artificial Chilomicrons in Men With Stable Coronary Heart Disease.

1-INTRODUCTION:

1.1.Chylomicron metabolism: Chylomicrons are particles formed in the postprandial period and are responsible for transporting blood lipids originating in the diet. These lipoproteins are formed mostly by a core of triglycerides (about 90% of its weight) and small amounts of vitamins and cholesterol esters, surrounded by a phospholipid monolayer. Its protein portion, ie apolipoproteins (apo) remain adhered to the surface of chylomicrons and do not exceed 2% of their total weight, the most common Apo E, CII and CIII, which modulate the activity of lipolytic enzymes or act as ligands for cell receptors.

In the circulation, chylomicrons bind to the endothelial surface of capillaries and triglyceride hydrolysis occurs by the action of lipoprotein lipase (LPL), thereby releasing fatty acids and glycerol to the surrounding cells, thus facilitating their absorption and accumulation in various tissues, especially adipose and muscle. The action of lipase is facilitated by apo CII on the particle surface . This mechanism is extremely important for the transit of energy in the body After this initial phase, the chylomicron remnants, smaller and depleted of triglycerides, are kidnapped in the Disse space and bind to receptors via the hepatic apolipoprotein E. Among these the investigators may mention the very LDL receptors (receptor B / E) and receiver RLP (receptor related protein in LDL). Importantly, apo B48, the main component of chylomicrons and remnants apoprotéico, has only a structural function. Chylomicrons and VLDL share common catabolic pathways regarding LPL and at least in part on the mechanisms of cellular uptake.

Within the classes of lipoproteins, chylomicrons to more rapid removal of plasma, and its half life of about 15 minutes in healthy men. The speed (kinetic) removal of chylomicrons from the circulation has been correlated with the incidence and severity of atherosclerotic injury. Several studies showed lower plasma clearance of chylomicrons in patients with coronary artery disease compared to individuals without atherosclerosis. These findings are found even in normolipemic subjects. Chylomicrons participate in the atherosclerotic process by the generation of foam cells by direct deposition of those remaining in the subendothelial space of arterial wall, and also interference with the reverse transport of colestero. Thus treatments that reduce the plasma concentration of chylomicrons by accelerating its catabolism plasma could be used to prevent atherosclerosis.

Among the methods used to evaluate the plasma kinetics of chylomicron, the investigators bring the lipid emulsion similar to chylomicrons labeled with radioisotopes. They offer an integrated vision and clear steps of the catabolism of chylomicrons in plasma. Several studies have shown that the kinetics of chylomicron is altered in patients with dyslipidemia and / or coronary artery disease (CAD). Defects were found both in lipolysis and the removal of chylomicron remnants, and in CAD patients these process were slowed5. Other studies have also shown that altered kinetics of chylomicrons is a marker of angiographic progression and a more severe course of CAD.