Abstract 333: Deficiency of CD40L Reduces the Incidence of Aortic Aneurysm Formation and Prevents Aortic Rupture
Deficiency of CD40L has been shown to inhibit atherosclerosis progression and to induce plaque stability. However, the effect of CD40L deficiency on other vascular diseases is largely unknown. Here we investigated the effects of CD40L deficiency on aortic aneurysm formation. ApoE−/ − (n=15) and CD40L−/ − /ApoE−/ − (n=16) mice (10 wks old) were treated for 4 wks with angiotensin II (1000ng/kg/min) which was delivered via osmotic minipumps, to induce suprarenal aortic aneurysms (AA). Most of the aneurysms showed features of dissection between media and adventitia. Interestingly, only 25% of the CD40L−/ − /ApoE−/ − mice developed an AA during angiotensin II infusion vs 67% of the ApoE−/ − mice (p<0.05). Moreover, in the ApoE−/ − group, mortality resulting from a ruptured AA was significantly higher than in the CD40L−/ − /ApoE−/ − group (27% vs 8%; p<0.05). Mean maximum aortic diameter was 2.76 ± 0.54 mm2 in ApoE−/ − mice and only 1.48 ± 0.38mm2 in CD40L−/ − /ApoE−/ − mice (p<0.05). Moreover, the number of medial elastin breaks decreased 76.4% in absence of CD40L (p<0.05). In the suprarenal aneurysm, only small initial atherosclerotic plaques were observed. Immunohistochemical analysis showed that macrophage, T-cell, and CD45+ cell infiltration in the aneurysmal aortic wall was reduced in CD40L−/ − ApoE−/ − mice, compared to ApoE−/ − mice. In conclusion, deficiency of CD40L protects against AA formation and reduces the incidence of aortic rupture, most likely by decreasing influx and activity of inflammatory cells, and by preventing expansion of the aortic wall.