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Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-07-2319. This Article Full Text (PDF) All Versions of this Article: 2003-07-2319v1 103/1/158    most recent Alert me when this article is cited Alert me if a correction is posted 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Diez-Juan, A. Articles by Andres, V. Search for Related Content PubMed PubMed Citation Articles by Diez-Juan, A. Articles by Andres, V. Social Bookmarking                   What's this? Submitted July 10, 2003 Accepted September 7, 2003 Selective inactivation of p27Kip1 in hematopoietic progenitor cells increases neointimal macrophage proliferation and accelerates atherosclerosis Antonio Diez-Juan, Paloma Perez, Miguel Aracil, David Sancho, Antonio Bernad, Francisco Sanchez-Madrid, and Vicente Andres* Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia-CSIC, Valencia, Spain Department of Oncology and Immunology, Centro Nacional de Biotecnologia-CSIC, Madrid, Spain Servicio de Inmunologia, Hospital de la Princesa, Madrid, Spain * Corresponding author; email: vandres{at}ibv.csic.es. Excessive proliferation of immune cells and vascular smooth myocytes (VSMCs) contribute to atherosclerosis. We have previously shown that whole-body inactivation of the growth suppressor p27 exacerbates atherosclerosis in apolipoprotein E-null mice (apoE-/-), and this correlated with increased proliferation of arterial macrophages and VSMCs. In the present study, we postulated that targeted disruption of bone marrow (BM) p27 is sufficient to enhance arterial macrophage proliferation and atherosclerosis. To test this hypothesis, sublethally irradiated apoE-/- mice with an intact p27 gene were transplanted with BM from either apoE-/- or p27-/-apoE-/- doubly deficient donor mice and challenged with a high-cholesterol diet. Compared with mice transplanted with apoE-/- BM, reconstitution with p27-/-apoE-/- doubly deficient marrow increased the expression of proliferating cell nuclear antigen in neointimal macrophages and accelerated aortic atherosclerosis, and this correlated with augmented aortic expression of the inflammatory cytokines CCL2/MCP-1 and CCL5/RANTES. Over all, these findings provide evidence that p27 deficiency in hematopoietic progenitor cells enhances the inflammatory/proliferative response induced by dietary cholesterol and accelerates atherosclerosis. 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