Angiotensin II Promotes Atherogenesis through upregulating the Expression of Connexin 43 in Dendritic Cells.
It is known, for a long time, that angiotensin II (Ang II) could contribute to atherogenesis (AS) and plaque vulnerability, however the underlying mechanisms are poorly understood. Dendritic cells (DCs) are critical for the development of both inflammation and atherogenesis. In the present study, we tried to investigate the influence of AngII on the expression of connexin43 (Cx43) in DCs, as well as the effect of AngII on AS. After mouse bone marrow&mdash;derived dendritic cells (BMDCs) were treated by Ang II with or without Valsartan, the expression of Cx43 was quantified by Western Blots. The expression of Cx43 and CD40 (one marker of DCs) of DCs derived from AS plaques of ApoE&mdash;/&mdash; mice was detected by immunohistochemistry double staining. The morphology of atherosclerotic plaque was indicated by immunohistochemistry staining of smooth muscle cells. The expression of Cx43 (P &lt; 0.05) was increased significantly in mouse BMDCs after treatment with AngII. In atherosclerotic plaques from ApoE&mdash;/&mdash; mice expressing high levels of endogenous AngII, upregulation of Cx43 (P &lt; 0.01) and CD40 (P &lt; 0.01) was observed. The upregulation and pro&mdash;atherogenesis effect of Cx43 could be blocked by the AngII type 1 receptor blocker Valsartan, both in vitro and in vivo. AngII may promote atherosclerosis and plaque vulnerability by increasing the expression of Cx43 in DCs and inducing the maturation of DCs through the angiotensin II type 1 receptor.