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VEGF : un biomarqueur potentiel dans la physiopathologie cardiovasculaire

Abstract : VEGF-A is involved in several diseases, including cardiovascular disease and several types of cancer. The existence of common signaling between the VEGF-A, cell adhesion molecules and inflammatory molecules may help to explain the wide range of functions of VEGF-A in different pathological situations. As part of this thesis, we have developed an integrative approach to study of VEGF-A and its position in several metabolic pathways. This approach involves the identification of genetic variants associated with VEGF-A and their biological function by a transcriptomic approach. Thus, the general aim of this thesis is to investigate the complex relationships between four polymorphisms associated with VEGF-A, its plasma levels and its expression with cell adhesion molecules, inflammatory molecules, plasma lipids, candidate genes (NOS3, CD14, MMP3 and IL-4) and with cardiovascular risk factors (obesity and blood pressure) in healthy individuals. For our studies, we used a subgroup of the STANISLAS Family Study and other populations available in the Biological Resources Center IGE-PCV. Our transcriptomics experiments have been performed with peripheral blood mononuclear cells. The results showed: •An association between VEGF-A145 isoform with the levels of ICAM-1 mRNA, L-selectin mRNA and TNF-[alpha] mRNA. •An association between the levels of VEGF-A and the levels of ICAM-1 and E selectin. •An epistatic interactions between the VEGF-A related variants for the levels of E selectin, TNF-[alpha], ICAM-1 and IL-6. •An association of rs4416670 with levels of mRNA of L selectin. •An association between rs6921438 and levels of HDL-C and LDL-C. •An interaction between rs4416670 and hypertension for the interindividual variation of apolipoprotein E. •Significant associations between the expression of VEGF-A with NOS3, CD14, MMP3, IL4R and IL-4 polymorphisms. •Significant epistatic interactions between genetic variants of NOS3, CD14, MMP3, IL4R, and IL4 and the four polymorphisms related to VEGF-A on the plasma levels of VEGF-A. •Significant interactions between rs1800779 in NOS3 and HDL-C, triglycerides, and obesity, as well as interactions of rs6921438 with hypertension on plasma levels of VEGF-A. •Significant associations and gene × blood lipids interactions between all genetic variants of VEGF-A with obesity traits. •A significant association between rs4416670 and pulse pressure. •An epistatic interaction between rs6921438 and rs10738760 on pulse pressure. •Significant associations between the rs10738760 variant of VEGF-A and the risk of metabolic syndrome. The results of this thesis indicate the central role of VEGF-A in the regulation of various physiological processes and offer VEGF-A as a potential novel biomarker for cardiovascular disease to be further evaluated clinically
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Submitted on : Thursday, March 29, 2018 - 1:18:26 PM
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Abdelsalam Saleh. VEGF : un biomarqueur potentiel dans la physiopathologie cardiovasculaire. Médecine humaine et pathologie. Université de Lorraine, 2015. Français. ⟨NNT : 2015LORR0017⟩. ⟨tel-01751394⟩



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