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      Platelets secrete stromal cell–derived factor 1α and recruit bone marrow–derived progenitor cells to arterial thrombi in vivo

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          The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow–derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34 + bone marrow cells and c-Kit + Sca-1 + Lin bone marrow–derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34 + and c-Kit + Sca-1 + Lin bone marrow–derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1α, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury.

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          Most cited references 30

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          Long-term lymphohematopoietic reconstitution by a single CD34-low/negative hematopoietic stem cell.

          Hematopoietic stem cells (HSCs) supply all blood cells throughout life by making use of their self-renewal and multilineage differentiation capabilities. A monoclonal antibody raised to the mouse homolog of CD34 (mCD34) was used to purify mouse HSCs to near homogeneity. Unlike in humans, primitive adult mouse bone marrow HSCs were detected in the mCD34 low to negative fraction. Injection of a single mCD34(lo/-), c-Kit+, Sca-1(+), lineage markers negative (Lin-) cell resulted in long-term reconstitution of the lymphohematopoietic system in 21 percent of recipients. Thus, the purified HSC population should enable analysis of the self-renewal and multilineage differentiation of individual HSCs.
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            HMG-CoA reductase inhibitors (statins) increase endothelial progenitor cells via the PI 3-kinase/Akt pathway.

            HMG-CoA reductase inhibitors (statins) have been developed as lipid-lowering drugs and are well established to reduce morbidity and mortality from coronary artery disease. Here we demonstrate that statins potently augment endothelial progenitor cell differentiation in mononuclear cells and CD34-positive hematopoietic stem cells isolated from peripheral blood. Moreover, treatment of mice with statins increased c-kit(+)/Sca-1(+)--positive hematopoietic stem cells in the bone marrow and further elevated the number of differentiated endothelial progenitor cells (EPCs). Statins induce EPC differentiation via the PI 3-kinase/Akt (PI3K/Akt) pathway as demonstrated by the inhibitory effect of pharmacological PI3K blockers or overexpression of a dominant negative Akt construct. Similarly, the potent angiogenic growth factor VEGF requires Akt to augment EPC numbers, suggesting an essential role for Akt in regulating hematopoietic progenitor cell differentiation. Given that statins are at least as potent as VEGF in increasing EPC differentiation, augmentation of circulating EPC might importantly contribute to the well-established beneficial effects of statins in patients with coronary artery disease.
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              Platelets in inflammation and thrombosis.

              For many years it has been known that platelets play an important role in thrombosis and hemostasis. In recent times, however, it has become evident that platelets also have relevant functions in inflammation. It was shown that thrombosis and inflammation share several key molecular mechanisms and in fact are 2 intrinsically linked processes. In this review, we intend to give a short overview with emphasis on work stemming from our laboratory.

                Author and article information

                J Exp Med
                The Journal of Experimental Medicine
                The Rockefeller University Press
                15 May 2006
                : 203
                : 5
                : 1221-1233
                [1 ]Deutsches Herzzentrum and Medizinische Klinik, Technical University of Munich, D-80636 Munich, Germany
                [2 ]Institute for Medical Microbiology, Immunology, and Hygiene, [3 ]Clinical Cooperation Group Vaccinology, National Research Center for Environment and Health (GSF), and [4 ]Institute of Pathology, Klinikum rechts der Isar, Technical University of Munich, D-81675 Munich, Germany
                [5 ]Procorde GmbH, D-82152 Martinsried, Germany
                [6 ]Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, LMU München, D-80336 Munich, Germany
                [7 ]Max-Planck Institute of Molecular Biomedicine, University of Münster, D-48149 Münster, Germany
                [8 ]Harvard Medical School, Children's Hospital, Boston, MA 02115
                [9 ]Institute for Biomedical Research, Birmingham University Medical School, Birmingham B15 2TT, England, UK
                [10 ]Innere Medizin III, Universität Tübingen, D-72076 Tübingen, Germany
                Author notes

                CORRESPONDENCE Steffen Massberg: massberg@ 123456cbr.med.harvard.edu

                Copyright © 2006, The Rockefeller University Press



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