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VEGF-A and intermediate phenotypes of cardiovascular diseases: a functional genomics approach

Abstract : Vascular endothelial growth factor (VEGF) is a multifunctional cytokine that has been linked to cardiovascular diseases (CVDs) and related predisposing statuses such as metabolic syndrome (MetS).The identification of genetic variants that influence the VEGF circulating levels and their associations with MetS and adhesion and inflammation molecules could enable us to have a comprehensive approach of the relationship of this molecule with CVDs. Therefore, we aimed at first to investigate the genetic background of VEGF levels, via a genome wide association analysis, and the pre-analytical and analytical variation factors of VEGF levels measurements before examining the implication of this molecule in inflammation and in MetS. Also, we examined the differences of MetS between Iranian (MASHHAD cohort) and French (STANISLAS cohort) populations. The main findings of this thesis are: 1) the identification of 4 genetic variants(rs6921438, rs4416670, rs6993770 and rs10738760) that explain 47.6% of circulating VEGF levels, 2) the associations of VEGF and its identified genetic variants with adhesion and inflammation molecules such as ICAM-1, E and L selectins , TNF-alpha, IL-6 and CRP at protein and transcription levels, 3) the association of VEGF-related polymorphism rs10738760 with MetS, 4) the relationship between VEGF regulatory variant, rs6921438, and LDL-C and HDL-C,5) the proposition of the best conditions for measuring both circulating VEGF (serum being the most stable anticoagulant) and its gene expression by reducing time between blood collection and centrifugation, and by avoiding multiple freeze-thaw cycles,6) a high prevalence of MetS in Iranian women. Our results propose the biological connections between VEGF, inflammation and adhesion molecules, lipids and MetS
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Mohsen Azimi Nezhad. VEGF-A and intermediate phenotypes of cardiovascular diseases: a functional genomics approach. Human health and pathology. Université de Lorraine, 2012. English. ⟨NNT : 2012LORR0067⟩. ⟨tel-01749291⟩



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