Atherosclerosis which accounts in Western Europe for more than 40 % of deaths, is a generalized disease that develops slowly and is symptomless until lesions have become sufficiently severe to cause myocardial or cerebral infarction. Research on specific and precocious markers of atherosclerosis and the development of non invasive techniques for their early detection represent major challenges in biomedical field. We hope that this volume of edited papers, a consequence of the third international colloquium on atherosclerosis, conducted at the University of Brussels, Belgium through the support of the "Fondation de Recherche sur l' AtherosclE, rose" will contribute to this goal. Among the topics discussed the major ones were the mechanism of action of lipolytic enzymes, the deficiency or dysregulation of cellular receptors, the genetic deficiencies of apolipoproteins, and the panoply of external factors as diet, physical exercise, drugs, which mOdify the lipoprotein metabolism. Special interest was also devoted to potent techniques as kinetic analysis of metabolic tracers and use of monoclonal antibodies. Their contribution to the detection and treatment of atherosclerosis will be obviously essential in the future.

The past two decades have seen steady progress in our understanding of the pathogenesis of atherosclerosis. The role of low density lipoprotein (LOL) increase and of LOL receptor deficiency or malfunctions in familial hypercholesterolemia has been largely enlightened by the works of Brown and Goldstein. These authors postulated also that modification of LOL to a form recognized by the scavenger or acetyl-LOL receptor may be required for lipid loading of macrophage-derived foam cells in the lesions. A growing body of evidence suggests that oxidative modification of LOL could enhance its atherogenicity by its implication as a factor in the generation of foam cells. Thus, if the role of LOL in the pathogenesis of hypercholesterolemia was well established a great deal of information appears currently on new approaches such as the mechanisms leading to the accumulation of foam cells, the impact of LOL structural alterations, notably oxidation and the role of gene mutations of apolipoprotein Band/or LOL receptor The opening topic is devoted to these new avenues outlined in the field of hypercholesterolemia. The first part concerns the genetic aspects of atherosclerosis: mainly the genetics of apo 1 ipoprote ins , their transcriptional regulation, the amino acid mutations of the apo B gene and of the LOL receptor gene, the structural domains and the acylation sites of apoprotein B.

Plasma lipoproteins constitute a unique macromolecular system of lipid-protein complexes responsible for the transport of lipids from their sites of origin to their sites of utilization either as metabolic fuel or as structural components of cell membranes. Although studies on the role of lipoproteins in the mechanism of lipid transport are meritorious in their own right, the ever-increasing interest in chemical and functional properties of this remarkable class of conjugated proteins stems from the impressive evidence of their direct involvement in the genesis and develop ment of atherosclerotic lesions. The initial emphasis on neutral lipids and phospholipids as the most characteristic constituents of operationally defined lipoprotein classes has shifted in recent years to their protein moieties or apolipoproteins. The discovery of a number of apolipoproteins and characterization of familial hypolipoproteinemias as apolipoprotein deficiency disorders indicated that apolipoproteins play an essential role in maintaining the structural stability and integrity of lipoprotein particles. In addition to their role in the formation of lipoproteins, apolipoproteins were shown to perform a variety of functions in metabolic conversion of lipoproteins and their interactions with cellular surfaces. Results from several laboratories have demonstrated that the chemical and metabolic heterogeneity of operationally-defined lipoprotein classes is due to the presence of several discrete lipoprotein particles with similar physical properties but different and characteristic apolipoprotein composition. Thus, the apolipoproteins have emerged not only as essential structural and functional constituents of lipoproteins but also as unique chemical markers for identifying and classifying lipoprotein particles."