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Blood, 1 January 2004, Vol. 103, No. 1, pp. 158-161. Prepublished online as a Blood First Edition Paper on September 22, 2003; DOI 10.1182/blood-2003-07-2319. This Article Full Text 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 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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Díez-Juan, A. Articles by Andrés, V. Search for Related Content PubMed PubMed Citation Articles by Díez-Juan, A. Articles by Andrés, V. Related Collections Hemostasis, Thrombosis, and Vascular Biology Immunobiology Phagocytes Oncogenes and Tumor Suppressors Brief Reports Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Brief report Selective inactivation of p27Kip1 in hematopoietic progenitor cells increases neointimal macrophage proliferation and accelerates atherosclerosis Antonio Díez-Juan, Paloma Pérez, Miguel Aracil, David Sancho, Antonio Bernad, Francisco Sánchez-Madrid, and Vicente Andrés From the Laboratory of Vascular Biology and the Hormone Action Laboratory, Department of Molecular and Cellular Pathology and Therapy, Instituto de Biomedicina de Valencia-CSIC, Spain; the Department of Oncology and Immunology, Centro Nacional de Biotecnología-CSIC, Campus Cantoblanco, and the Servicio de Inmunología, Hospital de la Princesa, Universidad Autónoma de Madrid, Madrid, Spain. Excessive proliferation of immune cells and vascular smooth myocytes (VSMCs) contributes 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 received a BM transplant from either apoE–/– or p27–/–apoE–/– doubly deficient donor mice and challenged with a high-cholesterol diet. Compared with mice that received an apoE–/– BM transplant, 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 (monocyte chemoattractant protein 1) and CCL5/RANTES (regulated on activation, normal T-cell expressed and secreted). Overall, these findings provide evidence that p27 deficiency in hematopoietic progenitor cells enhances the inflammatory/proliferative response induced by dietary cholesterol and accelerates atherosclerosis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. M. C. Dupasquier, E. Dibrov, A. L. Kneesh, P. K. M. Cheung, K. G. Y. Lee, H. K. Alexander, B. K. Yeganeh, M. H. Moghadasian, and G. N. Pierce Dietary flaxseed inhibits atherosclerosis in the LDL receptor-deficient mouse in part through antiproliferative and anti-inflammatory actions Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2394 - H2402. [Abstract] [Full Text] [PDF] L. S. M. Boesten, A. S. M. Zadelaar, A. van Nieuwkoop, L. Hu, J. Jonkers, B. van de Water, M. J. J. Gijbels, I. van der Made, M. P. J. de Winther, L. M. Havekes, et al. Macrophage retinoblastoma deficiency leads to enhanced atherosclerosis development in ApoE-deficient mice FASEB J, May 1, 2006; 20(7): 953 - 955. [Abstract] [Full Text] [PDF] S. Fasciano, R. C. Patel, I. Handy, and C. V. Patel Regulation of Vascular Smooth Muscle Proliferation by Heparin: INHIBITION OF CYCLIN-DEPENDENT KINASE 2 ACTIVITY BY p27kip1 J. Biol. Chem., April 22, 2005; 280(16): 15682 - 15689. [Abstract] [Full Text] [PDF] T. Kanda, K. Hayashi, S. Wakino, K. Homma, K. Yoshioka, K. Hasegawa, N. Sugano, S. Tatematsu, I. Takamatsu, T. Mitsuhashi, et al. Role of Rho-Kinase and p27 in Angiotensin II-Induced Vascular Injury Hypertension, April 1, 2005; 45(4): 724 - 729. [Abstract] [Full Text] [PDF] V. Andres Unexpected Proatherogenic Properties of p21: Beyond Cell Cycle Control? Circulation, December 21, 2004; 110(25): 3749 - 3752. [Full Text] [PDF] V. Andres Control of vascular cell proliferation and migration by cyclin-dependent kinase signalling: new perspectives and therapeutic potential Cardiovasc Res, July 1, 2004; 63(1): 11 - 21. [Abstract] [Full Text] [PDF]

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