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GW24-e2228 The role of CXCR4 on stem cell therapy for atherosclerosis
  1. Na Zhang,
  2. Jian-An Wang
  1. Department of Cardiology, Key Lab of Cardiovascular Disease, Second Affiliated Hospital of Zhejiang University School of Medicine

Abstract

Objectives The role of bone marrow-derived cells in atherosclerosis is controversial now, because of different cell types and delivery methods they used. It has been reported that calcium pretreatment can increase CXCR4 expression on BMCs and enhance their mobilisation and homing. But there are no direct evidences that the increase of CXCR4 expression can enhance their roles in atherosclerosis. In the present study, we assessed the contribution of CXCR4 to BMCs therapy for atherosclerosis in apolipoprotein E-deficient (ApoE-/-) mice.

Methods 12 weeks old ApoE-/- mice that fed 2 months high-fat diet beginning at 4 weeks served as recipients and ApoE-/- mice that constitutively express LacZ gene (ApoE-/-/ROSA) and ROSA mice in C57BL/6J background are donors. The recipients receiving intravenous injection of either freshly isolated or CaCl2 treated BMCs from ApoE-/-/ROSA or ROSA mice. After one week, the mice were sacrificed and quantitative assessed atherosclerotic lesion size, the level of serum cholesterol and cytokines, donor cells in the plaques.

Results We found that plaque size was significantly increased in mice receiving BMCs from ApoE-/-/ROSA mice compared with controls, and CaCl2 treatment group with higher increase, while mice receiving BMCs from ROSA mice had opposite results. The results were the same in serum cholesterol and IL-10, IL-6 levels in the plasma. And we found apoE protein in apo E-/- mice receiving ROSA BMCs.

Conclusions Transfer of WT BMCs can reduce atherosclerotic plaque size, whereas injection of ApoE-/- BMCs results in an increase in atherosclerotic lesion size. Increase CXCR4 expression of BMCs can enhance their different roles in the progression of atherosclerosis.

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