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The role of endothelial progenitor cells in arterial thrombosis and vascular remodeling observing the interference of dermatan sulfate, an antithrombotic glycosaminoglycan in this process

Grant number: 12/23640-2
Support Opportunities:Regular Research Grants
Duration: March 01, 2013 - February 28, 2015
Field of knowledge:Biological Sciences - Morphology - Cytology and Cell Biology
Principal Investigator:Cristina Pontes Vicente
Grantee:Cristina Pontes Vicente
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Associated researchers:Claudio Chrysostomo Werneck


Endothelial progenitor cells were first described by Asahara et al, 1997, and were isolated from humam peripheral blood. These cells are originated from bone marrow and can be characterized by the expression of CD34, CD133, VEGFR2 e CD31, CD144, Tie-2, LDL internalization and formation of tube like structures in vitro. They can be mobilized from bone marrow to peripheral blood going to the lesion site, differentiating into endothelial cells (EC) and promoting re-endothelization. They can also secrete molecules that inhibit smooth muscle cells proliferation and simulates adult endothelial cells proliferation. Arterial thrombosis can lead to vascular schemia and cardiac infartion. Recanalization of the thrombus is a part of the vascular bead recovery after lesion and is directly linked to the cells and molecules associated to the thrombus. Dermatan sulfate (DS) is a glycosaminoglycan (GAG) that can act as an antithrombotic, anticoagulant and anti-inflammatory drug inhibiting thrombus formation immediately after arterial lesion. In this work we will isolate a population of cells called endothelial progenitor cells (EPC) obtained from mice mononuclear bone marrow cells, expand then in vitro, verify their EPC characteristics, like high proliferation and the presence of their main immunophenotipic markers. Then, we are going to analyse if these cells are able to secrete growth factors and citokines that influence in the proliferation of adult mice EC and smooth mucle cells in culture. These cells are also going to be tested in an arterial thrombosis model using ferric chloride associated or not with DS treatment. Since DS can affect thrombosis directly as previously described by our group, we are going to verify if this GAG can interfere in EPC migration and association to the thrombus and its contribution to endothelial recovery after arterial lesion. (AU)

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Scientific publications (4)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
BRITO, MARLON V.; DE OLIVEIRA, CLEIDE; SALU, BRUNO R.; ANDRADE, SONIA A.; MALLOY, PAULA M. D.; SATO, ANA C.; VICENTE, CRISTINA P.; SAMPAIO, MISAKO U.; MAFFEI, FRANCISCO H. A.; OLIVA, MARIA LUIZA V.. The Kallikrein Inhibitor from Bauhinia bauhinioides (BbKI) shows antithrombotic properties in venous and arterial thrombosis models. THROMBOSIS RESEARCH, v. 133, n. 5, p. 945-951, . (09/53766-5, 12/23640-2)
VASSEQUI-SILVA, TALLITA; PEREIRA, DANIELLE SOUSA; NERY DIEZ, ANA CLAUDIA C.; BRAGA, GUILHERME G.; GODOY, JULIANA A.; MENDES, CAMILA B.; DOS SANTOS, LEONARDO; KRIEGER, JOSE E.; ANTUNES, EDSON; COSTA, FABIO T. M.; et al. Losartan and captopril treatment rescue normal thrombus formation in microfibril associated glycoprotein-1 (MAGP1) deficient mice. THROMBOSIS RESEARCH, v. 138, p. 7-15, . (10/19916-7, 12/23640-2)
CARNEIRO, GIANE D.; GODOY, JULIANA A. P.; WERNECK, CLAUDIO C.; VICENTE, CRISTINA P.. Differentiation of C57/BL6 mice bone marrow mononuclear cells into early endothelial progenitors cells in different culture conditions. Cell Biology International, v. 39, n. 10, p. 1138-1150, . (10/19916-7, 12/23640-2)
GODOY, JULIANA A. P.; CARNEIRO, GIANE D.; SIELSKI, MICHELI S.; BARBOSA, GUILHERME O.; WERNECK, CLAUDIO C.; VICENTE, CRISTINA P.. Combined dermatan sulfate and endothelial progenitor cell treatment: action on the initial inflammatory response after arterial injury in C57BL/6 mice. CYTOTHERAPY, v. 17, n. 10, p. 1447-1464, . (10/01119-3, 12/23640-2)

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