Full text
| |
| Author(s): |
Juliana Aparecida Preto de Godoy
Total Authors: 1
|
| Document type: | Doctoral Thesis |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia |
| Defense date: | 2014-08-29 |
| Examining board members: |
Cristina Pontes Vicente;
Arnaldo Rodrigues dos Santos Junior;
Helena Coutinho Franco de Oliveira;
Silvia Borges Pimentel de Oliveira;
Alexandre Bruni Cardoso
|
| Advisor: | Cristina Pontes Vicente |
| Abstract | |
Atherosclerosis is a disease that undertakes blood vessels by exacerbated atheroma plaque formation, and blocking blood flow. The most used surgical intervention in these cases is the angioplasty, however, this procedure can cause a lesion to the endothelium, where thrombotic and inflammatory processes are initiated, recruiting inflammatory cells to the lesion site and also promoting migration and adhesion of endothelial progenitor cells (EPC) in order to recovery endothelial damage. Glycosaminoglycans (GAGs), like dermatan sulfate (DS) and fucosilated chondroitin sulfate (FCS), are molecules that act as antithrombotic, anticoagulant and anti-inflammatory agents. EPC are cells that exist in bone marrow mononuclear (MNC) cells fraction population and can be involved in vascular repair. In this study, we analyzed the influence of DS and FCS and cellular therapy using EPC in inflammation and thrombosis after arterial lesion in wild-type (C57BL6) and apolipoprotein E deficient (ApoE-/-) mice. All animals were submitted to a surgical procedure in the left common carotid artery, mimicking the lesion caused by angioplasty in humans. Proteins/factors involved in the initial process after an endothelial lesion were analyzed by western blotting (ICAM-1, P-selectina, eNOS and SDF-1) and by Elisa (TNF-?, IL-10, SDF-1 and TGF-?); lesioned carotid artery were analyzed histologically to verify thrombus formation and gelatinase activity by zimography `in situ¿. All analyzes were done 1 and 3 days after arterial lesion. We observed that C57BL6 mice treatment with DS was able in decrease the initial inflammatory reaction and, at the same time, stimulate progenitor cells migration to the lesion site; this result was also observed in relation to FCS use, despite its did not prevent thrombus formation. Therapy using MNC alone or with DS or FCS increased the initial inflammatory response. Use of EPC also promoted this response but when used together with DS, we can obtain a decreased inflammatory response and, at the same time, an increased in the eNOS expression, improving vascular tonus. In ApoE-/- mice, treatments were not able in improving inflammatory response; treatment with EPC and FCS was the one with best action, decreasing inflammatory response and improving the vascular tonus. GAGs (DS or FCS) therapy was able to decrease the initial inflammation. Besides, MNC injection leads to an increase in inflammation probably due to its inflammatory characteristics. We conclude that GAGs can be acting quimio-atracting molecules to the cells and, at the same time, avoiding the initial thrombosis and inflammation after injury and they can be used as supporting agents in cellular therapy use to help in vascular recovery after injury (AU) | |
| FAPESP's process: | 10/01119-3 - Influence of glycosaminoglycans in the inflammatory process and cellular therapy using endothelial progenitor cells for recovery of mice arterial lesion. |
| Grantee: | Juliana Aparecida Preto de Godoy |
| Support Opportunities: | Scholarships in Brazil - Doctorate |