| First Author | Parks BW | Year | 2006 |
| Journal | Arterioscler Thromb Vasc Biol | Volume | 26 |
| Issue | 12 | Pages | 2703-9 |
| PubMed ID | 16990555 | Mgi Jnum | J:128044 |
| Mgi Id | MGI:3765399 | Doi | 10.1161/01.ATV.0000246774.02426.71 |
| Citation | Parks BW, et al. (2006) Loss of the lysophosphatidylcholine effector, G2A, ameliorates aortic atherosclerosis in low-density lipoprotein receptor knockout mice. Arterioscler Thromb Vasc Biol 26(12):2703-9 |
| abstractText | OBJECTIVE: Lysophosphatidylcholine is a major product of low-density lipoprotein (LDL) oxidation and secretory phospholipase A2-mediated lipid hydrolysis within atherosclerotic lesions. The G2A receptor mediates chemotaxis of cultured macrophages and T cells to lysophosphatidylcholine, supporting a pro-atherogenic role for this receptor in vivo. We investigated the ability of G2A to modulate atherosclerosis in mice. METHODS AND RESULTS: We measured atherosclerosis in G2A+/+ and G2A-/- LDL receptor knockout (LDLR-/-) mice. Consistent with a previous study, early lesion size at the aortic sinus was unaffected by G2A deficiency. However, G2A deficiency attenuated lesion progression at this site (42% to 44% reduction in average lesion area) and led to robust suppression of atherosclerosis throughout the aorta after short and extended periods of diet intervention (reduction in aortic lesion coverage: 62% to 73% at 9 weeks, 75% to 84% at 20 weeks). In G2A-/- LDLR-/- mice, intimal macrophage accumulation at lesion-prone sites of the aorta was significantly reduced in the absence of any detectable effect on T cell recruitment. Examination of lipoprotein profiles revealed elevated levels of circulating high-density lipoprotein (HDL) cholesterol in G2A-/- LDLR-/- mice compared with their G2A+/+ LDLR-/- counterparts after extended periods of diet intervention (54% increase in mean HDL cholesterol concentration). CONCLUSIONS: G2A provides a pro-atherogenic stimulus in vivo consistent with its chemotactic action but to which a pleiotropy of effects, including modulation of lipoprotein metabolism, may also contribute. |
