Class A scavenger receptors (SR-A) have been implicated in the atherogenic process, although there have been conflicting reports as to their specific effect on the development of lesions. In part, this discord may arise because of the variable contribution of SR-A in the several cell types known to express this
protein. To determine the effects of macrophage-specific SR-A expression in the atherogenic process, transgenic mice were created using the chicken
lysozyme (lyso) promoter to drive expression of bovine SR-A (bSR-A). To express this gene in an
atherosclerosis-susceptible strain, bone marrow cells from transgenic and non-transgenic littermates were used to repopulate lethally-irradiated female
LDL receptor (LDLr)(-/-) mice. Following hematopoietic engraftment, mice were placed on a diet enriched in saturated fat and
cholesterol. After 8 weeks, there was a modest, but statistically significant reduction in serum total
cholesterol in LDLr(-/-) mice repopulated with lyso-bSR-A transgenic cells, due to decreased
LDL-cholesterol. The extent of
atherosclerosis was reduced in both cross-sectional analysis of the aortic root and en face analysis of the intimal surface of the aortic arch. In addition to changes in
atherosclerosis, lyso-bSR-A repopulated LDLr(-/-) mice had a marked increase (3.6x) in spleen weights and a disruption of spleen white pulp formation. Therefore, macrophage-specific overexpression of SR-A resulted in reduced
atherosclerosis in two vascular beds, reduced serum
cholesterol concentrations, and changed the morphology of the spleen.