Plasmalogen phospholipids are involved in HDL-mediated cholesterol efflux: insights from investigations with plasmalogen-deficient cells.
Plasmalogens are ether-glycerophospholipids that exist in all mammalian cells, but their physiological function remains thus far an enigma. It has been previously suggested that the association of high-density lipoprotein (HDL) with cellular phospholipid is a pre-requisite for the process of HDL-mediated cholesterol efflux (HDL-MCE). To investigate our hypothesis that plasmalogens might play a role in HDL-MCE, we used a model composed of plasmalogen-deficient cells including RAW mutant macrophages and fibroblasts from patients with rhizomelic chondrodysplasia punctata type II. In mutant macrophages, HDL-MCE was reduced by 57% compared to control macrophages, after 16 hours. A similar phenomenon was observed in plasmalogen-deficient patients fibroblasts. Incubation of plasmalogen-deficient fibroblasts with 1-0-hexadecyl-sn-glycerol, which restored plasmalogen levels to that of control cells, resulted in a 35% increase in HDL-MCE, compared to a 10% increment in controls. The novel finding that HDL-MCE is reduced in plasmalogen-deficient cells and increases following plasmalogen restoration leads us to suggest that plasmalogen has an important function in the mediation of cellular cholesterol efflux.
Mandel
H
H
Department of Pediatrics, Rambam Medical Center, Haifa, Israel. h_mandel@rambam.health.gov.il
Sharf
R
R
Berant
M
M
Wanders
R J
RJ
Vreken
P
P
Aviram
M
M
D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D002784:Cholesterol / Q000378:metabolism*; D006801:Humans; D008075:Lipoproteins, HDL / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D051379:Mice; D010743:Phospholipids / Q000378:metabolism; D010955:Plasmalogens
D008075:Lipoproteins, HDL; D010743:Phospholipids; D010955:Plasmalogens; D002784:Cholesterol