HDL biology
CETP and LCAT localize mainly to LpA-I, not LpA-I:A-II, particles, a review finds, explaining why LpA-I promotes more cholesterol efflux (Atherosclerosis 1994)
Original title: Apolipoprotein A-I-containing particles and reverse cholesterol transport: evidence for connection between cholesterol efflux and atherosclerosis risk
ApoA-I-containing lipoproteins exist as two major families: those containing both apoA-I and apoA-II (LpA-I:A-II) and those with apoA-I but no apoA-II (LpA-I). Metabolic studies with radiolabeled particles suggest kinetic differences between these families, supporting distinct functional roles within HDL. Notably, the proteins that stimulate reverse cholesterol transport, lecithin:cholesterol acyltransferase (LCAT) and cholesteryl ester transfer protein (CETP), are mainly present in LpA-I rather than LpA-I:A-II. Long-term exposure to LpA-I promoted more cholesterol efflux than LpA-I:A-II in cell studies, and LpA-I:A-II could inhibit LpA-I-promoted efflux, supporting apoA-II as an antagonist of cholesterol efflux. In mice, apoA-I overexpression increased cholesterol efflux and protected C57BL/6 mice from atherosclerosis, while increased apoA-II expression appeared to decrease efflux and promote aortic fatty streak development.
Original abstract
It is now clearly established that apo A-I-containing lipoproteins exist as two major families, those containing apo A-I and apo A-II (LpA-I:A-II) and those containing apo A-I but free of apo A-II (LpA-I). Metabolic studies utilizing radiolabeled lipoprotein particles suggested that there is a kinetic difference between LpA-I and LpA-I:A-II family and support the concept that there may be important functional differences between the lipoprotein particles present within HDL. Of considerable significance was the finding that proteins stimulating reverse cholesterol transport (lecithin:cholesterol acyltransferase (LCAT), cholesteryl ester transfer protein (CETP)) are mainly present in LpA-I and not in LpA-I:A-II family. Cholesterol efflux mediated by A-I-containing particles has been studied in different cells. Long term exposure to LpA-I family promoted cholesterol efflux whereas less efflux was observed in the presence of LpA-I:A-II family. The fact that LpA-I:A-II family can inhibit the LpA-I promoted cholesterol efflux strongly supports the role of apo A-II as an antagonist in the production of cholesterol efflux. These results which emphasize that LpA-I and LpA-I:A-II families behave as distinct entities have been confirmed in other studies showing that they have different clinical significance. The results in mice transgenic for apo A-I indicate that overexpression of apo A-I induces more cholesterol efflux and protects C57BL/6 mice from atherosclerosis. Increased expression of apo A-II in mice appears to decrease cholesterol efflux and to promote rather than retard aortic fatty streak development.(ABSTRACT TRUNCATED AT 250 WORDS)
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.