Scavenger receptor deficiency leads to more complex atherosclerotic lesions in APOE3Leiden transgenic mice

Apolipoprotein (apo) E3Leiden is a dysfunctional apo E variant associated w ith familial dysbetalipoproteinemia in humans. Transgenic mice carrying the APOE3Leiden gene develop hyperlipidemia and are highly susceptible to diet -induced atherosclerosis. An early step in atherosclerosis is foam cell for mation, which is thought to result from the unrestricted uptake of modified lipoproteins by macrophages. To investigate the role of the macrophage sca venger receptor type I and II (MSR-A) in this process, APOE3Leiden transgen ic mice were crossed onto a MSR-A deficient background and the development of atherosclerosis was examined. In view of recent results with apo E defic ient mice (Suzuki H et al., A role for the macrophage scavenger receptors i n atherosclerosis. Nature 1997;386(6622):292-296), absence of the MSR-A in APOE3Leiden mice was expected to lead to a reduction of atherosclerosis. In our study we compared APOE3Leiden/MSR-A deficient mice (E3L MSR-A(-/-)) to APOE3Leiden/MSR-A wild-type mice (E3L MSR-A(+/+)). These animals were fed an atherogenic diet for 10 weeks. Quantification of the lesion area showed no significant difference between E3L MSR-A(-/-) and E3L MSR-A(+/+) mice al though there was a trend towards the development of larger lesions in the E 3L MSR-A(-/-) mice. All lesions were typed according to their cellular comp osition. In both male and female E3L MSR-A(-/-) mice, significantly more se vere lesions developed as compared to E3L MSR-A(+/+) mice. These results in dicate that the effect of MSR-A deficiency on atherogenesis may depend on t he presence or absence of apo E. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.