Kinetic Studies of the Metabolism of Rapidly Exchangeable Apolipoproteins May Leave Investigators and Readers With Exchangeable Results

Edward A. Fisher The Editors invited Dr Henry Ginsberg to review an important topic that is relevant to many kinetic studies of human lipoprotein metabolism, including one in the present issue. Changes in the concentration of a plasma protein are usually thought to involve the balance between its production and clearance, but as Drs Ginsberg and Ramakrishnan point out, in the case of exchangeable apolipoproteins, the change in concentration associated with a particular fraction of plasma lipoproteins may not be from production or clearance. We welcome any editorial correspondence on this issue. Department of Medicine (Cardiology) NYU School of Medicine 522 First Ave. New York, NY 10016 edward.fisher@med.nyu.edu In this issue of ATVB , Chan et al present interesting results of a study of the effects of atorvastatin and fenofibrate on apolipoprotein CIII (apoCIII) metabolism.1 Each drug was administered alone, and the study was conducted as a 3-way crossover design with placebo. The authors report that both drugs reduced plasma and very low-density lipoprotein (VLDL) apoCIII. Further, they conclude from their tracer kinetic studies that the fall in VLDL apoCIII levels resulted from increased fractional catabolic rates (FCR) and reduced production rates (PR) of VLDL apoCIII. These results, they note, may provide an insight into the triglyceride-lowering effects of both atorvastatin and fenofibrate, because apoCIII inhibits both lipoprotein lipase activity and removal of remnants via receptor-mediated pathways.See accompanying article on page 1831 A close reading of the article raises issues, …