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Effects of nitric oxide donors on MMPs production and activity in endothelial cells

Grant number: 11/11597-2
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2011
Effective date (End): June 30, 2014
Field of knowledge:Biological Sciences - Pharmacology - Cardiorenal Pharmacology
Grantee:Cesar Arruda Meschiari
Home Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil


The pathophysiology of cardiovascular diseases (CVD) is polygenic and multifactorial involving morphological and functional changes in the cardiovascular system associated with various factors, including decreased bioavailability of nitric oxide and vascular remodeling, which are involved in the activity of extracellular matrix metalloproteinases (MMPs). Some studies in cultured cells suggest that NO donors can reduce the expression of MMPs, and also NO synthase inhibitors can increase the expression of MMPs. Although NO was decreased and increased MMPs during CVD, there is clear evidence that levels of NO can directly modulate the activity of MMPs in the cardiovascular system. Also it is not known whether this effect would be mediated by NF-kB, nor is this effect is dependent on guanylate cyclase activity (which promotes the formation of cyclic GMP). Thus, this project aims to study whether I) the effect of NO donors might decrease the concentrations and activity of MMPs in endothelial cells stimulated by phorbol myristate acetate (PMA) (a well-know inducer of MMP-9) and II) the effect of NO synthese inhibitors might increase the concentrations and activity of MMPs in endothelial cells. In case we observed these effects described in I and II, we intend to determine whether those effects are mediated by the activation of NF-kB or by intracellular cGMP level. (AU)

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
MESCHIARI, Cesar Arruda. Inhibitory effects of NO-GMPc pathway stimulating drugs on MMP-9 production by endothelial cells. 2014. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Medicina de Ribeirão Preto (PCARP/BC) Ribeirão Preto.

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