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Analysis of initial inflammatory reaction after arterial injury in wild-type and atherosclerotic mice treated with dermatan sulfate.

Grant number: 10/15267-4
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): November 01, 2010
Effective date (End): October 31, 2011
Field of knowledge:Biological Sciences - Biology
Principal Investigator:Cristina Pontes Vicente
Grantee:Flávio Oliveira Higino
Host Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Endothelial lesion promotes various effects in blood vessels such as coagulation, thrombosis and inflammation. These factors can affect the proliferation, migration and differentiation of endothelial cells, smooth muscle cells and inflammatory cells at the site where it occurred, leading to pathological process development such as inflammation and neointima formation, that can causes blood vessel stenosis. Besides, in situations where the atherosclerotic process is already presente, it can increase atheroma plaques formation. The recovery of endothelial lesions depends on the inhibition of inflammatory reaction, smooth muscle cells proliferation and also on the capacity of the endothelial cells to proliferate at the injury site. It is known that circulating endothelial progenitor cells (EPC) are cells with ability to differentiate into mature endothelial cells helping in neovasculogenesis and in citocines production that may lead to an increase in the local endothelial cells proliferation at the injury site, promoting the endothelium recovery. Dermatan sulfate (DS) is a glycosaminoglycan that presents antithrombotic, anticoagulant and antiinflammatory activities. This glycosaminoglycan can also helps in the establishment of a better microenvironment, where the EPC can migrate and proliferate in a more efficient manner. This project intends to study the role of DS administration in the initial inflammatory process after arterial lesion, verifying its capacity in increasing the circulating endothelial cells migration to the site of arterial lesion and in the recovery of the endothelium lesion. To make this study, we will analyze the concentration of some factors such as TGF-² and the presence and expression of proteins such as p-SMAD-3, ICAM-1, SDF-1, VEGF and eNOS. Besides, we will study the proliferation of endothelial cells, smooth muscle cells and circulating EPC in the injury site in presence or absence of DS. The determination of these factor can help explain the mechanisms involved in endothelium recovery in the first moments after arterial lesion and also help developing new therapeutic strategies for cardiovascular diseases such as the use of DS as a assistant drug in vascular therapy.

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