Abstract 173: Upregulation of Sema7A Induced by Disturbed Flow Contributes to the Development of Atherosclerosis
Background: Atherosclerosis preferentially develops in areas of arteries with arches and branches, where the flow is disturbed (D-flow). D-flow upregulates proatherogenic genes and promotes the dysfunctional endothelial cell phenotype. Semaphorin 7A (Sema7A), a membrane-associated glycosylphosphatidylinositol (GPI)-linked cell-surface glycoprotein, was recently found to be expressed in the endothelial cells and played important roles in several pathophysiological processes. We hypothesize that Sema7A is involved in the proatherogenic process induced by D-flow. Methods and Results: We performed partial carotid ligation (PCL) on C57BL/6 mice by ligation of the external carotid artery (ECA), internal carotid artery (ICA), and ophthalmic artery (OA) of the left carotid artery (LCA), leaving the superficial temporal artery (STA) untied. The ultrasound image was used to monitor blood flow. Successful partial ligation was obtained as blood flow velocity was reduced by 70% (n=3) and D-flow was generated in the LCA while the blood flow in RCA remained normal. After 48h ligation, mice were sacrificed and total RNA was isolated from carotid arteries for the analysis of Sema7A gene expression by real-time PCR. Results showed that Sema7A expression in the LCA was 2.6-fold higher (P=0.0237, n=3) in D-flow condition compared to RCA. To ask whether Sema7A is involved in D-flow-induced atherosclerosis, we generated Sema7A-/-ApoE-/- mice and Sema7A+/+ApoE-/- mice, and performed PCL at 2 weeks on high fat diet. The results showed that atherosclerotic lesion size in the LCA under disturbed condition was decreased by 50.74% (P=0.0072) in ApoE-/-Sema7A-/- mice (0.2411±0.05265%, n=6) compared to Sema7A+/+ApoE-/- control mice (0.4894 ± 0.05186%, n=6). Conclusion: Our data showed that D-flow promotes the upregulation of Sema7A gene expression in endothelial cells. Deletion of Sema7A attenuates atherosclerotic plaque formation induced by D-flow.
Author Disclosures: F. Yang: None. S. Hu: None. C. Tang: None. L. Zhu: None.
- © 2015 by American Heart Association, Inc.