Hypercholesterolaemia and circulating levels of CXC chemokines in apoE*3 Leiden mice.

Hyperlipidaemia may accelerate the development of atherosclerosis by enhancing the expression of chemokines by cells within the arterial wall. Chemokines of the CC subfamily are clearly implicated in atherogenesis; however, recent reports suggest that CXC chemokines may play a hitherto unrecognised role in monocyte recruitment into atheromatous lesions expressing these molecules. Here, we examine whether circulating levels of CXC chemokines may reflect the pathogenic changes occurring during early atherogenesis. ApoE*3 Leiden mice developed marked hypercholesterolaemia, and early Type I 'fatty streak' lesions, following consumption of an atherogenic diet high in saturated fat and cholesterol, and containing sodium cholate, for up to 4 weeks. By contrast, their non-transgenic littermates (C57BL/6J) exhibited a much less pronounced hypercholesterolaemia and did not develop fatty streak lesions, when fed the same diet. Under these conditions, serum concentrations of CXC chemokines, KC and Macrophage Inflammatory Protein-2 (MIP-2) were significantly (P