The role of CD27-CD70-mediated T cell co-stimulation in vasculogenesis, arteriogenesis and angiogenesis. (1st June 2018)

• Record Type: Journal Article
• Authors: Simons, K.H.; Aref, Z.; Peters, H.A.B.; Welten, S.P.; Nossent, A.Y.; Jukema, J.W.; Hamming, J.F.; Arens, R.; de Vries, M.R.; Quax, P.H.A.
• Is Part Of: International journal of cardiology. Volume 260(2018)
• Page Start: 184
• Page End: 190
• Publication Date: 2018-06-01
• Subjects: Neovascularization -- Co-stimulation -- T cell -- CD70 -- Arteriogenesis -- Angiogenesis; Cardiology -- Periodicals; Electronic journals; 616.12
• DOI: 10.1016/j.ijcard.2018.02.015
• Languages: English
• ISSNs: 0167-5273

Abstract

Abstract: Background: T cells have a distinctive role in neovascularization, which consists of arteriogenesis and angiogenesis under pathological conditions and vasculogenesis under physiological conditions. However, the role of co-stimulation in T cell activation in neovascularization has yet to be established. The aim of this study was to investigate the role T cell co-stimulation and inhibition in angiogenesis, arteriogenesis and vasculogenesis. Methods and results: Hind limb ischemia was induced by double ligation of the left femoral artery in mice and blood flow recovery was measured with Laser Doppler Perfusion Imaging in control, CD70 −/−, CD80/86 −/−, CD70/80/86 −/− and CTLA4 +/− mice. Blood flow recovery was significantly impaired in mice lacking CD70 compared to control mice, but was similar in CD80/86 −/−, CTLA4 +/− and control mice. Mice lacking CD70 showed impaired vasculogenesis, since the number of pre-existing collaterals was reduced as observed in the pia mater compared to control mice. In vitro an impaired capability of vascular smooth muscle cells (VSMC) to activate T cells was observed in VSMC lacking CD70. Furthermore, CD70 −/−, CD80/86 −/− and CD70/80/86 −/− mice showed reduced angiogenesis in the soleus muscle 10 days after ligation. Arteriogenesis was also decreased in CD70 −/− compared to control mice 10 and 28 days after surgery. Conclusions: The present study is the first to describe an important role for T cell activation via co-stimulation in angiogenesis, arteriogenesis and vasculogenesis, where the CD27-CD70 T cell co-stimulation pathway appears to be the most important co-stimulation pathway in pre-existing collateral formation and post-ischemic blood flow recovery, by arteriogenesis and angiogenesis.