Fractional efflux and net change in cellular cholesterol content mediated by sera from mice expressing both human apolipoprotein AI and human lecithincholesterol acyltransferase genes》.pdfVIP

Atherosclerosis 147 (1999) 227–235 locateatherosclerosis Fractional efflux and net change in cellular cholesterol content mediated by sera from mice expressing both human apolipoprotein AI and human lecithin:cholesterol acyltransferase genes Natalie Fournier a,b,*, Ve´ronique Atger b, Jean-Louis Paul a,b, Margarita de la Llera Moya c, George Rothblat c, Nicole Moatti a,b a Laboratoire de Biochimie Applique´e, Faculte´ des Sciences Pharmaceutiques et Biologiques, Chaˆtenay-Malabry, France b Laboratoire de Biochimie, Hoˆpital Broussais, 96 rue Didot, F -75674 Paris Cedex 14, France c Department of Biochemistry, MCP Hahnemann School of Medicine, Philadelphia, USA Received 31 July 1998; received in revised form 22 March 1999; accepted 27 April 1999 Abstract Human lecithin:cholesterol acyltransferase (LCAT) is a key enzyme in the metabolism of cholesterol and is postulated to participate in the physiological process called reverse cholesterol transport. We have used transgenic mice (Tgm) expressing either both human apolipoprotein AI (apo AI) and human LCAT genes or only the human apo AI gene (HuAILCAT or HuAI Tgm, respectively) to assess the consequences of LCAT overexpression on serum lipid and lipoprotein profiles and on the ability of each serum to promote bidirectional flux of cholesterol between serum and Fu5AH hepatoma cells. Mean serum LCAT activity of HuAILCAT Tgm was 2-fold increased compared to the HuAI group (48 9 vs. 24 5 nmolml per h, P 0.01 for HuAILCAT and HuAI Tgm, respectively) and the cholesterol esterification rate