| First Author | Bursill CA | Year | 2010 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 30 |
| Issue | 9 | Pages | 1773-8 |
| PubMed ID | 20702809 | Mgi Jnum | J:179548 |
| Mgi Id | MGI:5302630 | Doi | 10.1161/ATVBAHA.110.211342 |
| Citation | Bursill CA, et al. (2010) High-density lipoproteins suppress chemokines and chemokine receptors in vitro and in vivo. Arterioscler Thromb Vasc Biol 30(9):1773-8 |
| abstractText | OBJECTIVE: To investigate whether high-density lipoproteins (HDLs) suppress chemokine (CCL2, CCL5, and CX(3)CL1) and chemokine receptor (CCR2 and CX(3)CR1) expression, a mechanism for the atheroprotective properties of HDLs. METHODS AND RESULTS: Apolipoprotein (apo) E(-/-) mice were fed a high-fat diet for 12 weeks. Before being euthanized, the mice received 5 consecutive daily injections of lipid-free apoA-I, 40 mg/kg, or saline (control). The injection of apoA-I reduced CCR2 and CX(3)CR1 expression in plaques compared with controls (P<0.05). ApoA-I-injected mice had lower plasma CCL2 and CCL5 levels. Hepatic CCL2, CCL5, and CX(3)CL1 levels were also reduced (P<0.05). In vitro studies found that reconstituted HDL (rHDL) reduced monocyte CCR2 and CX(3)CR1 expression and inhibited their migration toward CCL2 and CX(3)CL1 (P<0.05). Preincubation with rHDL reduced CCL2, CCL5, and CX(3)CL1 expression in monocytes and human coronary artery endothelial cells. The stimulation of CX(3)CR1 with peroxisome proliferator-activated receptor gamma agonist CAY10410 was suppressed by preincubation with rHDL but did not affect the peroxisome proliferator-activated receptor gamma antagonist (GW9664)-mediated increase in CCR2. In monocytes and human coronary artery endothelial cells, rHDL reduced the expression of the nuclear p65 subunit, IkappaB kinase activity, and the phosphorylation of IkappaBalpha (P<0.05). CONCLUSIONS: Lipid-free apoA-I and rHDL reduce the expression of chemokines and chemokine receptors in vivo and in vitro via modulation of nuclear factor kappaB and peroxisome proliferator-activated receptor gamma. |
