Browsing by Author "Staels, Bart"
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- Fingolimod treatment modulates PPARγ and CD36 gene expression in women with multiple sclerosisPublication . Ferret-Sena, Véronique; Capelo, Carlos; Macedo, Ana; Salgado, António Vasco; Derudas, Bruna; Staels, Bart; Sena, ArmandoFingolimod is an oral immunomodulatory drug used in the treatment of multiple sclerosis (MS) that may change lipid metabolism. Peroxisome proliferator-activated receptors (PPAR) are transcription factors that regulate lipoprotein metabolism and immune functions and have been implicated in the pathophysiology of MS. CD36 is a scavenger receptor whose transcription is PPAR regulated. The objective of this study was to evaluate whether fingolimod treatment modifies PPAR and CD36 gene expression as part of its action mechanisms. Serum lipoprotein profiles and PPAR and CD36 gene expression levels in peripheral leukocytes were analysed in 17 female MS patients before and at 6 and 12 months after fingolimod treatment initiation. Clinical data during the follow-up period of treatment were obtained. We found that fingolimod treatment increased HDL-Cholesterol and Apolipoprotein E levels and leukocyte PPARγ and CD36 gene expression. No correlations were found between lipid levels and variations in PPARγ and CD36 gene expression. PPARγ and CD36 variations were significantly correlated during therapy and in patients free of relapse and stable disease. Our results suggest that PPARγ and CD36-mediated processes may contribute to the mechanisms of action of fingolimod in MS. Further studies are required to explore the relation of the PPARγ/CD36 pathway to the clinical efficacy of the drug and its involvement in the pathogenesis of the disease.
- Natalizumab treatment modulates Peroxisome Proliferator-Activated Receptors expression in women with multiple sclerosisPublication . Ferret-Sena, Véronique; Silva, Alexandra Maia e; Sena, Armando; Cavaleiro, Inês; Vale, José; Derudas, Bruno; Chinetti-Gbaguidi, Giulia; Staels, BartPeroxisome Proliferator-Activated Receptors (PPAR) are transcription factors suggested to be involved in inflammatory lesions of autoimmune encephalomyelitis and multiple sclerosis (MS). Our objective was to assess whether Natalizumab (NTZ) therapy is associated with alterations of PPAR expression in MS patients. We analyzed gene expression of PPAR in peripheral blood mononuclear cells (PBMC) as well as blood inflammatory markers in women with MS previously medicated with first-line immunomodulators (baseline) and after NTZ therapy. No differences in PPAR𝛼, PPAR𝛽/𝛿, PPAR𝛾, and CD36 mRNA expression were found in PBMC between patients under baseline and healthy controls. At three months, NTZ increased PPAR𝛽/𝛿 mRNA (𝑝 = 0.009) in comparison to baseline, while mRNA expression of PPAR𝛾 and CD36 (a well-known PPAR target gene) was lower in comparison to healthy controls (𝑝 = 0.026 and 𝑝 = 0.028, resp.). Although these trends of alterations remain after six months of therapy, the results were not statistically significant. Osteopontin levels were elevated in patients (𝑝 = 0.002) and did not change during the follow-up period of NTZ