title: Opposing effects of apolipoprotein m on catabolism of apolipoprotein B-containing lipoproteins and atherosclerosis.
abstract: BACKGROUND
  Plasma apolipoprotein (apo)M is mainly associated with high-density lipoprotein (HDL). HDL-bound apoM is antiatherogenic in vitro. However, plasma apoM is not associated with coronary heart disease in humans, perhaps because of a positive correlation with plasma low-density lipoprotein (LDL).
  
  
  OBJECTIVE
  We explored putative links between apoM and very-low-density (VLDL)/LDL metabolism and the antiatherogenic potential of apoM in vivo.
  
  
  RESULTS
  Plasma apoM was increased approximately 2.1 and approximately 1.5 fold in mice lacking LDL receptors (Ldlr(-/-)) and expressing dysfunctional LDL receptor-related protein 1 (Lrp1(n2/n2)), respectively, but was unaffected in apoE-deficient (ApoE(-/-)) mice. Thus, pathways controlling catabolism of VLDL and LDL affect plasma apoM. Overexpression (approximately 10-fold) of human apoM increased (50% to 70%) and apoM deficiency decreased ( approximately 25%) plasma VLDL/LDL cholesterol in Ldlr(-/-) mice, whereas apoM did not affect plasma VLDL/LDL in mice with intact LDL receptors. Moreover, plasma clearance of apoM-enriched VLDL/LDL was slower than that of control VLDL/LDL in mice lacking functional LDL receptors and LRP1, suggesting that apoM impairs the catabolism of VLDL/LDL that occurs independently of the LDL receptor and LRP1. ApoM overexpression decreased atherosclerosis in ApoE(-/-) (60%) and cholate/cholesterol-fed wild-type mice (70%). However, in Ldlr(-/-) mice the antiatherogenic effect of apoM was attenuated by its VLDL/LDL-raising effect.
  
  
  CONCLUSIONS
  The data suggest that defect LDL receptor function leads to increased plasma apoM concentrations, which in turn, impairs the removal of VLDL/LDL from plasma. This mechanism opposes the otherwise antiatherogenic effect of apoM.
authors.affiliation: Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Christoffersen
authors.forename: Tanja Xenia
authors.initials: TX
authors.lastname: Pedersen
authors.forename: Philip L S M
authors.initials: PL
authors.lastname: Gordts
authors.forename: Anton J M
authors.initials: AJ
authors.lastname: Roebroek
authors.forename: Björn
authors.initials: B
authors.lastname: Dahlbäck
authors.forename: Lars Bo
authors.initials: LB
authors.lastname: Nielsen
mesh_terms: D000818:Animals; D001053:Apolipoproteins / Q000172:deficiency / Q000235:genetics / Q000494:pharmacology*; D001055:Apolipoproteins B / Q000378:metabolism* / Q000494:pharmacology; D001057:Apolipoproteins E / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D050197:Atherosclerosis / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D015243:Cholesterol, VLDL / Q000097:blood; D003433:Crosses, Genetic; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D008079:Lipoproteins, VLDL / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000172:deficiency / Q000235:genetics; D014280:Triglycerides / Q000097:blood
chemical_list: D001053:Apolipoproteins; D001055:Apolipoproteins B; D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D015243:Cholesterol, VLDL; D008079:Lipoproteins, VLDL; D011973:Receptors, LDL; D014280:Triglycerides; D002784:Cholesterol