[Lipoprotein Lp(a) and CETP (cholesterol ester transfer protein): contribution of transgenic mice]

Lipoprotein Lp(a) is a pluri-molecular complex rich in cholesterol and composed of an LDL (low-density lipoprotein) particle to which is attached a large glycoprotein, apolipoprotein(a) (apo(a)). Numerous epidemiological studies have established a strong correlation between plasma levels of Lp(a) and the premature development of atheromatous vascular disease in man, an association which has subsequently been confirmed by the detection of Lp(a) in human atherosclerotic plaques. Furthermore, a marked structural resemblance has been demonstrated between apo(a) and plasminogen, a key protein of the fibrinolytic system and responsible for dissolution of blood clots. This discovery has provided evidence, for the first time, that Lp(a) might constitute an important link between atherosclerosis and thrombosis. Intense research effort is now underway to provide further understanding of (I) the structural organisation of the Lp(a) particle; (II) the molecular genetics of apo(a); (III) the processes involved in the synthesis, assembly intravascular metabolism and degradation of Lp(a) and apo(a); (IV) the nature of the interactions of Lp(a) and apo(a) with cellular and non-cellular components of the arterial wall; (V) the role of Lp(a) in fibrinolysis, and (VI) the relationship between Lp(a) and certain metabolic disorders such as familial hypercholesterolemia. These fascinating questions will be examined in the light of studies of different models of transgenic mce expressing human apo(a) alone, or both apo(a) and apo B100. In man, CETP assures the transfer of cholesteryl ester from high-density lipoproteins (HDL) to lipoproteins containing apo-B, and notably VLDL, IDL and LDL.(ABSTRACT TRUNCATED AT 250 WORDS)