Impact of MTHFR rs1801133, MTHFR rs1801131 and ABCB1 rs1045642 polymorphisms with increased susceptibility of rheumatoid arthritis in the West Algerian population: A case-control study.

Rheumatoid arthritis (RA) is an autoimmune disease that results in a chronic systemic inflammation. A few genetic epidemiologic studies found a potential association between genetic polymorphisms C677T (rs1801133) and A1298C (rs1801131) of methylenetatrahydrofolate reductase (MTHFR) gene and C3435T (rs1045642) of ATP-Binding cassette (ABCB1) gene and the increased risk for RA. The aim of this case-control study was to determine the relationship between these polymorphisms and RA susceptibility in West Algerian population. The dataset of the current study is composed of 110 RA patients and 101 healthy controls. All samples were genotyped for theses polymorphisms by TaqMan® allelic discrimination assay. Data were compared between cases and controls by the calculation of the odds ratio (OR) with a confidence interval at 95%. After age and RA erosion-stratified analyzes, no differences in genotypes or alleles frequencies distribution were found for MTHFR C677T (rs1801133) and ABCB1 C3435T (rs1045642) polymorphisms between RA cases and controls. However, the MTHFR A1298C (rs1801131) polymorphism presented a significant distribution in RA with age ≥ 40 (Genotypic data: p=0.007, OR=13.53[1.44-63.31], Allelic data: p=0.001, OR=2.39[1.39-4.1]), and in RA erosive form (Genotypic data: p=0.002, OR=6.92[1.68-30.23], Allelic data: p=0.0001, OR=2.43[1.54-3.85]).These results were confirmed after the Bonferroni correction. In this study we have showed, for the first time in the West Algerian population, that the MTHFR A1298C (rs1801131) polymorphism can be associated with rheumatoid arthritis.

Therapeutic effect of fucoidan-stimulated endothelial colony-forming cells in peripheral ischemia.

BACKGROUND: Fucoidan, an antithrombotic polysaccharide, can induce endothelial colony-forming cells (ECFC) to adopt an angiogenic phenotype in vitro. OBJECTIVES: We evaluated the effect of fucoidan on vasculogenesis induced by ECFC in vivo. METHODS: We used a murine hindlimb ischemia model to probe the synergic role of fucoidan-treatment and ECFC infusion during tissue repair. RESULTS: We found that exposure of ECFC to fucoidan prior to their intravenous injection improved residual muscle blood flow and increased collateral vessel formation. Necrosis of ischemic tissue was significantly reduced on day 14, to 12.1% of the gastronecmius cross-sectional surface area compared with 40.1% in animals injected with untreated-ECFC. ECFC stimulation with fucoidan caused a rapid increase in cell adhesion to activated endothelium in flow conditions, and enhanced transendothelial extravasation. Fucoidan-stimulated ECFC were resistant to shear stresses of up to 21 dyn cm(-2). Direct binding assays showed strong interaction of fucoidan with displaceable binding sites on the ECFC membrane. Bolus intramuscular administration of fucoidan 1 day after surgery reduces rhabdomyolysis. Mice injected with fucoidan (15 mg kg(-1)) had significantly lower mean serum creatine phosphokinase (CPK) activity than control animals. This CPK reduction was correlated with muscle preservation against necrosis (P < 0.001). CONCLUSIONS: Fucoidan greatly increases ECFC-mediated angiogenesis in vivo. Its angiogenic effect would be due in part to its transportation to the ischemic site and its release after displacement by proteoglycans present in the extracellular matrix. The use of ECFC and fucoidan together, will be an efficient angiogenesis strategy to provide therapeutic neovascularization.

Neoangiogenesis induced by progenitor endothelial cells: effect of fucoidan from marine algae.

Fucoidans--sulphated polysaccharides extracted from brown algae--could be beneficial in patients with ischemic diseases. Their antithrombotic and proangiogenic properties promote in animals, neovascularization and angiogenesis which prevent necrosis of ischemic tissue. In 1997, endothelial progenitor cells were first identified in human peripheral blood. They are recruited from bone marrow and contribute to neovascularization after ischemic injury. Mobilization of these cells in ischemic sites is an important step in new vessel formation. It is thought that the progenitors interact with endothelial cells, then extravasate and reach ischemic sites, where they proliferate and differentiate into new blood vessels. Although chemokines, cytokines and adhesion molecules are thought to be involved, the precise mechanism of progenitor mobilization is not fully understood. Recent studies suggest that stromal-derived factor 1 plays a critical role at several steps of progenitor mobilization. Given the role of proteoglycans within bone marrow, at the endothelium surface, and in growth factor and chemokine binding, fucoidans might influence the mobilization of endothelial progenitor cells and their incorporation in ischemic tissue. This review provides an update on circulating endothelial progenitors and their role in neovascularization. It focuses on recent advances in our understanding of interactions between these progenitor cells and exogenous sulphated polysaccharides, and their implications for understanding the fucoidan mechanism of action.