Submitted on January 11, 2005
Revised on February 15, 2005
Accepted on February 24, 2005
ESI-MS quantitation of increased sphingomyelin in Niemann-Pick disease type B HDL
Lee Ching Yin, Alain Lesimple, Åsmund Larsen, Orval Mamer, and Jacques Genest
Department of Medicine, McGill University, Montreal, Quebec H3A 1A1
Corresponding Author: jacques.genest{at}muhc.mcgill.ca
HDL have been proposed to have antiatherogenic properties because of their role in reverse cholesterol transport as lipid acceptors. In order to elucidate the phospholipid profile of these particles, we used electrospray ionization mass spectrometry (ESI-MS) to examine the phosphatidylcholine (PC) and sphingomyelin (SM) composition of HDL purified from plasma and nascently generated in vitro from fibroblasts. We also quantitatively compared the phospholipids present in these lipoproteins between normal and Niemann-Pick type B (NPD-B) diseased subjects characterized by sphingomyelinase (SMase) deficiency. We demonstrated that plasma HDL from NPD-B were significantly enriched in SM by an average of 28%, particularly the palmitoyl SM (with an increase of 95%) which accounted for approximately 25-44% of total SM molecular species. Similarly, we observed an increase of approximately 63% in total SM levels in the nascent HDL prepared from NPD-B fibroblasts. While PC levels in nascent HDL were comparable between control and NPD-B cells, there was a 95% increase in the total PC levels similar to that of SM in plasma HDL extracted from NPD-B subjects. These data provide insight into the structure of HDL and identify potential new roles for SMase in lipoprotein metabolism.
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