Impact of factors related to the expression of hypoxia (HIF1 and VEGF), lipid meta...
| Grant number: | 12/19653-1 |
| Support type: | Scholarships in Brazil - Doctorate |
| Effective date (Start): | June 01, 2013 |
| Effective date (End): | February 29, 2016 |
| Field of knowledge: | Health Sciences - Medicine |
| Principal Investigator: | Claudia Regina Bonini Domingos |
| Grantee: | Lidiane de Souza Torres |
| Home Institution: | Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil |
Abstract Sickle cell disease (SCD) is the term for hereditary anemias with presence of hemoglobin (Hb) S. It involves homozygous for Hb S (sickle cell anemia) and its association with other variants or thalassemia. The SCD is usually more severe in patients with Hb SS, followed by Hb S / beta-thalassemia, Hb SC and Hb SD, however, the clinical manifestations can be variable between individuals of the same genotype. The primary event responsible by the SCD complications is the polymerization of Hb S, followed by vascular occlusion, which corresponds to the main inflammatory stimulus of the disease and is associated with clinical complications such as vasculopathies. Several pro-inflammatory cytokines are elevated in the disease, and an exacerbated inflammatory response can result in tissue hypoxia and angiogenesis stimulation. Many studies are conducted about sickle cell anemia, but for other genotypes of DF the studies are scarce. The aim of this study is to analyze the processes of inflammation, angiogenesis and hypoxia in SCD - Hb SS, Hb S / beta-thalassemia, Hb SC and Hb D genotypes, aiming to understand the mechanisms that modulate the disease phenotype. We will evaluate pro-inflammatory markers (TNF-±, TGF-², IL-1² and IL-8), the anti-inflammatory (ANXA1) marker, angiogenic marker (VEGF) and hypoxia marker (HIF-1±), in these patients, comparing the results to a control group without hemoglobinopathies. Genetic polymorphisms in these markers will be analyzed by PCR-RFLP, while the plasma measurements will be performed by immunoassay in ELISA and multiplex analysis in Magpix technology. It is expected that polymorphisms screened contribute to the individual variations in plasma levels of biomarkers and it is possible to derive a relationship between the presence of these polymorphisms and the genotypes of SCD. | |