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Evaluation the role of lipoproteins in sickle cell disease

Grant number: 15/09671-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): January 01, 2016
Effective date (End): July 31, 2018
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Kleber Yotsumoto Fertrin
Grantee:Felipe Vendrame
Host Institution: Centro de Hematologia e Hemoterapia (HEMOCENTRO). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil


The haemoglobinopathies are diseases that result from mutations in the genes that encode the globin chains that make up hemoglobin, among which stand out in the Brazilian population, diseases sickle. They are characterized by chronic hemolytic anaemia, painful crises of vaso-occlusion and target organ damage caused by the polymerization of HbS within the erythrocytes and hemolysis, which leads to the release of plasma free hemoglobin molecules. The free heme group, resulting from the degradation of hemoglobin molecule, is deleterious and generates oxidative stress, vasoconstriction by consumption of nitric oxide, activation and endothelial cell dysfunction and recruitment of inflammatory cells, resulting in cellular and tissue damage. The important mechanisms that aim to minimize the effects of free heme in the human body are performed by haptoglobin, hemopexin, albumin, ±1 microglobulin and lipoproteins. Lipoproteins LDL and HDL are proteins that has the highest affinity for heme, and believes that they can serve as first "line of defense" to avoid damage caused by free heme until it can be transferred to the hemopexin and degraded. Considering the shortage of studies on relationship between heme and lipoproteins in sickle disease and by the existence of therapeutic measures able to modify the concentrations of circulating lipoproteins, the focus of this project is to characterize the production of lipoproteins and of free heme in blood samples of patients with sickle disease patient and, subsequently, investigate in cell culture model in vitro and in a transgenic murine model if the modulation of this production may represent a new therapeutic strategy against the excess of free heme vaso-oclusion process involved in these diseases.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
VENDRAME, Felipe. Evaluation of the role of lipoproteins in sickle cell disease. 2018. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas Campinas, SP.

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