Effects of direct infusion of bone marrow-derived progenitor cells and indirect mobilization of hematopoietic progenitor cells on atherosclerotic plaque and inflammatory process in atherosclerosis

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• 作者：Dimitris Tousoulis ; Alex ; ros Briasoulis ; Georgia Vogiatzi ; Aggeliki Valatsou ; Polina Kourkouti ; Alkistis Pantopoulou ; Nikolaos Papageorgiou ; Despina Perrea ; Christodoulos Stefanadis
• 关键词：Progenitor cells ; Atherosclerotic plaque ; Inflammation ; Ischemia
• 刊名：International Journal of Cardiology
• 出版年：12 October, 2013
• 年：2013
• 卷：168
• 期：5
• 页码：4769-4774
• 全文大小：904 K

文摘

Background

We sought to investigate the effects of lin 鈭?sca + cells, endothelial progenitor cells (EPCs) and granulocyte colony-stimulating factor (G-CSF) administration on atherosclerotic plaque progression.

Methods

Apolipoprotein E-deficient (apoE^{鈭?鈭?/sup>) mice were splenectomized and treated with high-cholesterol diet for 6 weeks in order to induce atherosclerotic plaque development. Bone marrow-derived Lin 鈭?sca-1 + cells were isolated and further cultured to early growth endothelial progenitor cells (EPCs). Mice were divided in four groups (n = 10/group) and received two intravenous injections of 5 脳 105 cells (lin 鈭?sca-1 + or EPCs), or granulocyte colony-stimulating factor (G-CSF 100 渭g/kg/day) for 7 days or normal saline. The same interventions were administered to animals, which had undergone unilateral hind-limb ischemia. Effects on inflammatory parameters, lesion severity, and atherosclerotic plaque area size were assessed.}

Results

The administration of both G-CSF and progenitor cells significantly decreased the levels of IL-6, 6 weeks after the initiation of treatment. Atherosclerotic lesion area was reduced by G-CSF (atherosclerotic plaque area percentage 22.94% 卤 3.68, p = 0.001), by lin 鈭?sca-1 + (23.27% 卤 5.98, p = 0.002) and cultured EPCs (23.16 卤 4.86%, p = 0.002) compared to control (32.75% 卤 7.05). In the atherosclerotic mice that underwent limb ischemia, the atherosclerotic plaque area, was not significantly different between the treatment groups cultured EPCs-treated mice and the control group (p = NS, for all).

Conclusions

Direct infusion of progenitor cells and indirect mobilization of hematopoietic progenitor cells decreased plaque progression and levels of inflammatory molecules in a murine model of atherosclerosis. Treatment with G-CSF, lin 鈭?sca-1 +, or EPCs may exert beneficial effects on vascular inflammation and atherosclerotic plaque progression. However, the effects are diminished in an ischemic setting.