doi: 10.1161/ATVBAHA.108.174185
© 2008 American Heart Association, Inc.
Editorials |
Kinetic Studies of the Metabolism of Rapidly Exchangeable Apolipoproteins May Leave Investigators and Readers With Exchangeable Results
From the Departments of Medicine (H.N.G.) and Pediatrics (R.R.), Columbia University College of Physicians and Surgeons, New York.
Correspondence to Henry Ginsberg, Columbia University College of Physicians and Surgeons, PH10-305, 680 West 168th St, New York, NY 10032. E-mail hng1@columbia.edu
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
An extract of the first 250 words of the full text is provided, because this article has no abstract. |
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, however, concerning the interpretation and reporting of apolipoprotein production rates when the apolipoprotein being studied is rapidly exchanging between lipoproteins; apoCIII is such an exchangeable apolipoprotein.2 Early studies with radio-iodinated lipoproteins as a source of apoCIII tracer demonstrated similar fractional removal rates of apoCIII in VLDL and HDL,3,4 indicative of rapid exchange of apoCIII between those two lipoproteins. Using radio-iodinated lipoproteins, we found evidence that there were both exchangeable and nonexchangeable pools of apoCIII in both VLDL and HDL.5 We also found very similar FCRs for apoCIII in VLDL and HDL, suggesting, at the least, a common exit from plasma for all apoCIII. Cohn et al presented kinetic data after infusion of deuterated leucine that supported incomplete
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