Abstract 3716: Endothelial-specific Deletion Of The Gap Junction Protein Connexin43 Reduces Atherosclerosis In Mice
Decreasing the expression of the gap junction protein connexin43 (Cx43) in mice provides beneficial effects on both the progression and composition of the atherosclerotic lesions. During atherosclerotic lesion development, Cx43 expression is temporarily up-regulated in intimal smooth muscle cells, induced in macrophages close to the lipid core and triggered in a subset of endothelial cells covering the shoulder of atherosclerotic lesions. The purpose of this study was to examine the role of endothelial Cx43 in the development of atherosclerosis in vivo. For this purpose, we have used the Cre-loxP system to create an atherosclerosis-susceptible mouse line in which Cx43 is deleted from the endothelium only. The natural progression of atherosclerosis and the composition of the atherosclerotic lesions were studied in 18 month-old male TIE2Cre+ Cx43fl/fl ApoE−/− mice and TIE2Cre- Cx43fl/fl ApoE−/− littermate controls. Body weights were not different between both groups. Interestingly, the progression of atherosclerosis (measured as % of surface stained with Sudan IV) was significantly reduced in the thoracic-abdominal aorta of TIE2Cre+ Cx43fl/fl ApoE−/− mice (21.53±7.14%; N=4) compared with TIE2Cre- Cx43/fl/fl ApoE−/− controls (46.84±11.60%, N=6, P<0.05). In addition, advanced atheroma in TIE2Cre+ Cx43fl/fl ApoE−/− mice contained less lipids and showed decreased calcium deposition compared with lesions in TIE2Cre- Cx43fl/fl ApoE−/− controls. Thus, endothelial-specific deletion of Cx43 in mice provides beneficial effects on both the natural progression and composition of the atherosclerotic lesions. Future studies are aimed at obtaining insight into the participation of Cx43 in macrophages and smooth muscle cells in atherosclerosis.