This Article Full Text Full Text (PDF) All Versions of this Article: 99/8/E74    most recent 01.RES.0000246095.90247.d4v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Wassmann, S. Articles by Nickenig, G. Search for Related Content PubMed PubMed Citation Articles by Wassmann, S. Articles by Nickenig, G. Related Collections Endothelium/vascular type/nitric oxide Mechanism of atherosclerosis/growth factors Other Vascular biology Animal models of human disease Genetically altered mice

Improvement of Endothelial Function by Systemic Transfusion of Vascular Progenitor Cells

From the Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Germany.

Correspondence to Dr Sven Wassmann, Medizinische Klinik und Poliklinik II, Universitätsklinikum Bonn, Sigmund-Freud-Str. 25, D-53105 Bonn, Germany. E-mail sven.wassmann{at}uni-bonn.de

Endothelial dysfunction is characterized by abnormalities in vasoreactivity and is a marker of the extent of atherosclerosis. Cellular repair by circulating progenitor cells of ongoing vascular injury may be essential for vascular integrity and function and may limit abnormalities in vasoreactivity. Apolipoprotein E–deficient (apoE^–/–) mice were splenectomized and treated with high-cholesterol diet for 5 weeks, resulting in marked impairment of endothelium-dependent vasodilation of aortic segments as compared with wild-type mice. Intravenous transfusion of 2x10⁷ spleen-derived mononuclear cells (MNCs) isolated from wild-type mice on 3 consecutive days restored endothelium-dependent vasodilation in the apoE^–/– mice, as measured 7, 14, and 45 days after transfusion. Histological analyses of aortic tissue identified fluorescent-labeled, exogenously applied progenitor cells that expressed the endothelial cell marker CD31 in the endothelial cell layer of atherosclerotic lesions. Progenitor cell treatment led to increased vascular nitric oxide synthase activity. Transfusion of either in vitro-differentiated Dil-Ac-LDL/lectin-positive endothelial progenitor cells, CD11b-positive (monocyte marker), CD45R-positive (B-cell marker), or Sca-1–positive (stem cell marker) MNC subpopulations significantly improved endothelium-dependent vasodilation, although these treatments were not as effective as transfusion of total MNCs. Depletion of MNCs of either CD11b-positive, CD45R-positive, or Sca-1–positive cells resulted in significant attenuation of endothelium-dependent vasodilation as compared with nondepleted MNCs; however, vasoreactivity was still significantly improved as compared with saline-treated apoE^–/– mice. Intravenous transfusion of spleen-derived MNCs improves endothelium-dependent vasodilation in atherosclerotic apoE^–/– mice, indicating an important role of circulating progenitor cells for the repair of ongoing vascular injury. More than 1 subpopulation of the MNC fraction seems to be involved in this effect.

Key Words: endothelial progenitor cells • apolipoprotein E–deficient mice • endothelial function • stem cells • nitric oxide