Abstract 5: Disruption of Semaphorin 7A Confers Protection against the Development of Atherosclerosis
Background: Atherosclerosis is an inflammatory disease of which both innate immunity and adaptive immunity are involved. Increasing evidence suggests that Semaphorin7A (Sema7A), a membrane-associated glycosylphosphatidylinositol (GPI)-linked cell-surface glycoprotein, plays important roles in the immune system and participates in several pathophysiological processes. Whether Sema7A participates in the progress of atherosclerosis is still unclear. Here we investigated the role of Sema7A in the development of atherosclerosis using the Sema7A-deficient mice that have been crossed with atherosclerosis-prone mice. Methods and Results: Atherosclerosis-prone ApoE-/- mice were crossed with Sema7A-/- mice to generate Sema7A-/- ApoE-/- mice and Sema7A+/+ ApoE-/- mice. After 12 weeks on high fat diet, mice were sacrificed and atherosclerotic plaque size was analyzed by en face preparation following Sudan IV Red staining. Although Sema7A deletion did not change mouse blood lipid profile, atherosclerotic lesion size in the whole aorta was decreased by 51.18% (P=00024) in Sema7A-/-ApoE-/- mice (5.01±1.04%, n=13) compared to Sema7A+/+ApoE-/- control mice (10.26±1.15%, n=13). When the aortic root was analyzed using Oil Red O staining, plaque formation was reduced by 45.96% (P=0.0016) in Sema7A-/-ApoE-/- mice (15.80±2.78%, n=7) compared to Sema7A+/+ApoE-/- control mice (31.09±2.56%, n=7). Immunohistochemical studies showed that macrophages within aortic root plaques were significantly reduced by 58.437% (P=0.0010) in ApoE-/- Sema7A-/- mice (24.68±2.767%, n=14) compared with Sema7A+/+ApoE-/- control mice (59.38±4.273%, n=14). Further studies showed a significant decrease in CD4+ cells by 51.31% (P<0.0001) and dendritic cells by 60.4% (P<0.0001), respectively, in the aortic roots in ApoE-/- Sema7A-/- mice compared to ApoE-/- mice. Additionally, Sema7A-/-ApoE-/- mice showed significantly higher collagen content (P<0.0022) and vulnerability index (P <0.0001) than Sema7A+/+ApoE-/- mice. Conclusion: These results demonstrate that genetic deletion of Sema7A delayed the formation of atherosclerotic plaque formation, likely by impairment of the accumulation of macrophages, T cells and dendritic cells in vascular wall.
Author Disclosures: S. Hu: None. F. Yang: None. C. Tang: None. L. Zhu: None.
- © 2015 by American Heart Association, Inc.