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| Author(s): |
Marcela Franco Mineiro
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2013-07-30 |
| Examining board members: |
Maria Heloisa de Souza Lima Blotta;
Maria Cristina Oliveira Izar;
José Roberto Matos Souza
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| Advisor: | Maria Heloisa de Souza Lima Blotta; Rômulo Tadeu Dias de Oliveira |
| Abstract | |
The presence of IL-1? and IL-18 in atherosclerotic lesions and their important role in endothelial activation, cell recruitment and switch to Th1 response, are indirect indications of the involvement of NLRs in disease pathogenesis. In this study we investigated the presence of mRNA and protein of various NLRs, AIM2, caspase-1, adaptor protein ASC and IL-1? in human atherosclerotic plaques. We observed that atheroma samples from asymptomatic patients had higher mRNA relative expression of NLRP1, NLRP2, NLRP3, NLRC2, NLRC3, NLRC4, NLRC5, NAIP and ASC. Risk factors have no influence in mRNA expression for any of them. Immunohistochemistry technique revealed the presence of NLRP1, NLRP3, AIM-2, NLRC2, NLRC3, NLRC5 and caspase-1, especially among macrophages, giant cells and foam cells. The presence of cholesterol crystals in monocytes and macrophages cultures stimulated with LPS, had an additive effect on IL-1? production. On the other hand, pharmacological inhibitors inhibited this cytokine production by THP-1 cells stimulated with cholesterol crystals. The ability of IL-1?to induce inflammatory mediators production by smooth muscle cells and endothelial cells was also evaluated. Cathepsin S, MMP3, CXCL10, CXCL16 and CX3CL1 were produced only by smooth muscle cells after stimulation, but CCL2, CXCL8 and CCL5 were produced by both smooth muscle cells and endothelial cells. In conclusion, our study revealed the presence of various NLRs mRNA and protein in human atherosclerotic plaques. Furthermore, we demonstrated the role of cholesterol crystals in the activation of IL-1? producers monocytes and macrophages, probably due to NLRP3 expressed in large amounts on the lesions analyzed. Finally, stimulation of smooth muscle cells and endothelial cells highlighted the importance of IL-1? as an inflammatory and destabilizing agent in lesions, confirming its potential as a therapeutic target that could restrain the prevailing inflammation in atherosclerosis (AU) | |
| FAPESP's process: | 11/05372-8 - Evaluation of NOD-like-receptors in human atherosclerotic plaques |
| Grantee: | Marcela Franco Mineiro |
| Support Opportunities: | Scholarships in Brazil - Master |