Therapeutic strategies to address the consequences of hemoglobin decompartmentalization in hemolytic disorders

• Grant number: 12/16903-7
• Support Opportunities: Scholarships abroad - Research
• Start date: January 01, 2013
• End date: December 31, 2013
• Field of knowledge: Health Sciences - Medicine - Medical Clinics
• Principal Investigator: Jose Eduardo Tanus dos Santos
• Grantee: Jose Eduardo Tanus dos Santos
• Host Investigator: Mark T. Gladwin
• Host Institution: Faculdade de Medicina de Ribeirão Preto (FMRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Institution abroad: University of Pittsburgh (Pitt), United States

Abstract

Nitric oxide (NO) is important for cardiovascular health and its bioavailability depends on the balance between NO synthesis and NO degradation. There is evidence indicating that increased plasma free hemoglobin concentrations impair NO bioavailability causing endothelial dysfunction, increased adhesion molecule expression, platelet activation and the formation of reactive oxygen species. The physiological reaction rates between NO and hemoglobin are small because hemoglobin is confined to erythrocytes. However, intravascular hemolysis increases NO consumption and impaired NO/cGMP pathway signaling. Therefore, therapeutic strategies aiming at improving NO concentrations (NO donors, eNOS stimulators, cGMP degradation inhibitors) have been proposed as alternatives to prevent the complications associated with hemoglobin decompartmentalization. We aimed at testing new small molecules (drugs and peptides) that bind to the heme portion of hemoglobin promoting its clearance or blocking its reaction with NO as possible therapies to improve NO bioavailability. (AU)