Last Updated: 06/06/2024
Role of kinins and angiotensins in chronic inflammation and vascular dysfunction during severe malaria
Objectives
*Original title in Portuguese: Papel de cininas e angiotensinas na inflamação crônica e disfunção vascular durante a malária grave
In this project the murine model of P. berghei ANKA malaria will be used to evaluate the effects of the components of the Renin-Angiotensin (SAR) and kallikrein-kinin (SCC) systems in the establishment of severe malaria, focusing on inflammatory properties, endothelial dysfunction and evolution of the host immune response.
Malaria caused by Plasmodium falciparum is considered the most severe and fatal form of the disease in humans, inducing more than half a million deaths per year. The clinical symptoms of severe disease include: high parasite load (> 5%), hypoglycaemia, seizures, repeated vomiting, anemia, acute renal failure, hepatic dysfunction, pulmonary edema, hemoglobinuria, hemorrhagic and coagulation disorders, and cerebral malaria (MC ). CM is a complex neurological syndrome and represents a major public health problem. Malaria-associated kidney disease has also been considered a death factor in infected patients. The mechanisms of pathogenesis of severe disease are not yet established, but it is well accepted that it depends on both the parasite and host factors, in this case, including the sequestration of infected erythrocytes in the microvasculature, host immune response, endothelial dysfunction and edema formation. Understanding the molecular mechanisms involved in these parasite / host interactions will facilitate the determination of key elements for a possible therapeutic intervention. In addition, the results obtained here can be extrapolated in the context of other parasitic diseases.
Feb 2019 — Feb 2022
