The major findings of this study are, first, that Rgs1 is upregulated in atherosclerotic vessels and in AAA, is low in circulating monocytes but is greatly upregulated in response to activation and macrophage differentiation (Fig. 7); second, that Rgs1 deficiency increases macrophage chemotaxis and reduces chemokine receptor homologous desensitization; and third, Rgs1 deficiency protects against early atherosclerotic plaque and aortic aneurysm rupture in ApoE−/− mice, due to reduced accumulation of leukocytes in the artery wall. This evidence concerns the gene RGS1 and triple-A syndrome.