BACKGROUND: T lymphocytes, components of the immune and inflammatory systems, are involved in such normal processes as wound healing and host defense against infection and in such pathological processes as tumor growth and atherosclerotic plaque development. Angiogenesis is a mechanism common to each. Because CD4+ T lymphocytes are active in regulating humoral and cellular responses of the immune system, we determined whether CD4+ cells contribute to collateral vessel development by using the mouse ischemic hindlimb model. METHODS AND RESULTS: One week after ischemia, CD4-/- mice showed reduced collateral flow induction, macrophage number, and vascular endothelial growth factor levels in the ischemic muscle compared with wild-type mice. There was also delayed recovery of hindlimb function and increased muscle atrophy/fibrosis. Spleen-derived purified CD4+ T cells infused into CD4-/- mice selectively localized to the ischemic limb and significantly increased collateral flow as well as macrophage number and vascular endothelial growth factor levels in the ischemic muscle. Muscle function and damage also improved. CONCLUSIONS: These results indicate an important role of CD4+ cells in collateral development, as demonstrated by a 25% decrease in blood flow recovery after femoral artery ligation. Our data also suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenic cytokines.
BACKGROUND: T lymphocytes, components of the immune and inflammatory systems, are involved in such normal processes as wound healing and host defense against infection and in such pathological processes as tumor growth and atherosclerotic plaque development. Angiogenesis is a mechanism common to each. Because CD4+ T lymphocytes are active in regulating humoral and cellular responses of the immune system, we determined whether CD4+ cells contribute to collateral vessel development by using the mouse ischemic hindlimb model. METHODS AND RESULTS: One week after ischemia, CD4-/- mice showed reduced collateral flow induction, macrophage number, and vascular endothelial growth factor levels in the ischemic muscle compared with wild-type mice. There was also delayed recovery of hindlimb function and increased muscle atrophy/fibrosis. Spleen-derived purified CD4+ T cells infused into CD4-/- mice selectively localized to the ischemic limb and significantly increased collateral flow as well as macrophage number and vascular endothelial growth factor levels in the ischemic muscle. Muscle function and damage also improved. CONCLUSIONS: These results indicate an important role of CD4+ cells in collateral development, as demonstrated by a 25% decrease in blood flow recovery after femoral artery ligation. Our data also suggest that CD4+ T cells control the arteriogenic response to acute hindlimb ischemia, at least in part, by recruiting macrophages to the site of active collateral artery formation, which in turn triggers the development of collaterals through the synthesis of arteriogenic cytokines.
Authors: Jason U Tilan; Lindsay M Everhart; Ken Abe; Lydia Kuo-Bonde; Dan Chalothorn; Joanna Kitlinska; Mary Susan Burnett; Stephen E Epstein; James E Faber; Zofia Zukowska Journal: FASEB J Date: 2013-03-01 Impact factor: 5.191
Authors: Robert S Crawford; Hassan Albadawi; Alessandro Robaldo; Michael A Peck; Christopher J Abularrage; Hyung-Jin Yoo; Glenn M Lamuraglia; Michael T Watkins Journal: J Surg Res Date: 2013-03-15 Impact factor: 2.192
Authors: Hendrik B Sager; Ralf Middendorff; Kim Rauche; Joachim Weil; Wolfgang Lieb; Heribert Schunkert; Wulf D Ito Journal: J Angiogenes Res Date: 2010-09-16
Authors: Daniel P Sieveking; Patrick Lim; Renée W Y Chow; Louise L Dunn; Shisan Bao; Kristine C Y McGrath; Alison K Heather; David J Handelsman; David S Celermajer; Martin K C Ng Journal: J Exp Med Date: 2010-01-13 Impact factor: 14.307