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Etude des effets de la protéine C-réactive sur certains aspects de la biologie des cellules mononucléées circulantes et des monocytes humains : Implications pour la physiopathologie des maladies cardiovasculaires

Abstract : C-reactive protein is now considered as an essential biomarker for predicting the occurrence of cardiovascular diseases and their acute complications through mechanisms that are not fully elucidated. We investigated CRP effects on several aspects of the biology of ex vivo human peripheral blood mononuclear cells (PBMC) and monocytes. In fact, these cells can be involved in the pathophysiology of these diseases. Also, we used the promonocytic line THP-1. These three cellular types were incubated with purified or recombinant CRP and gene expression of pro-inflammatory cytokines, chemokines and (pro)MMP-9 was analysed by real time semi-quantitative PCR and protein expression by immunometric or ELISA tests. CRP doesn't seem to act upon neither the tested cytokines synthesis nor the (pro)MMP-9 expression. A global approach by protein array with the cultured monocytes supernatants showed that CRP induced VEGF-A protein synthesis. This result was confirmed at transcriptional level by RT-PCR and at protein level by ELISA. A complementary study with the monocytic cell line THP-1 demonstrated the activation of PI3-Kinase and MEK pathways but not of p38MAPKinase pathway in this regulation. These results provide insight into several mechanisms that could transform the statistical association between CRP and cardiovascular diseases into a cause-to-effect relationship. Some of these mechanisms could represent therapeutic targets for cardiovascular diseases.
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https://hal.univ-lorraine.fr/tel-01748512
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Gaëlle Bello. Etude des effets de la protéine C-réactive sur certains aspects de la biologie des cellules mononucléées circulantes et des monocytes humains : Implications pour la physiopathologie des maladies cardiovasculaires. Médecine humaine et pathologie. Université Henri Poincaré - Nancy 1, 2008. Français. ⟨NNT : 2008NAN10104⟩. ⟨tel-01748512⟩

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