| First Author | Christoffersen C | Year | 2010 |
| Journal | Circ Res | Volume | 106 |
| Issue | 10 | Pages | 1624-34 |
| PubMed ID | 20360257 | Mgi Jnum | J:172136 |
| Mgi Id | MGI:5004749 | Doi | 10.1161/CIRCRESAHA.109.211086 |
| Citation | Christoffersen C, et al. (2010) Opposing effects of apolipoprotein m on catabolism of apolipoprotein B-containing lipoproteins and atherosclerosis. Circ Res 106(10):1624-34 |
| abstractText | RATIONALE: 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. METHODS AND 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. CONCLUSION: 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. |
