Abstract
Angiotensin II, a peptide hormone that regulates blood pressure, has been proposed as a protective factor against cerebral malaria based on a genetic analysis. In vitro studies have documented an inhibitory effect of angiotensin II on Plasmodium growth, while studies using chemical inhibitors of angiotensin II in mice showed protection against experimental cerebral malaria but not major effects on parasite growth. To determine whether the level of angiotensin II affects Plasmodium growth and/or disease outcome in malaria, elevated levels of angiotensin II were induced in mice by intradermal implantation of osmotic mini-pumps providing constant release of this hormone. Mice were then infected with P. berghei and monitored for parasitemia and incidence of cerebral malaria. Mice infused with angiotensin II showed decreased parasitemia seven days after infection. The development of experimental cerebral malaria was delayed and a moderate increase in survival was observed in mice with elevated angiotensin II, as confirmed by decreased number of cerebral hemorrhages compared to controls. The results presented here show for the first time the effect of elevated levels of angiotensin II in an in vivo model of malaria. The decreased pathogenesis observed in mice complements a previous human genetic study, reinforcing the hypothesis of a beneficial effect of angiotensin II in malaria.
Highlights
Malaria is still a major public health problem world wide, causing more than 200 million cases per year and approximately 600,000 deaths, mostly in African children [1]
To first characterize the anti-Plasmodium effect of Ang Angiotensin II (II), the activity of Angiotensin II (Ang II) was tested against P. falciparum cultures in vitro
To determine whether Ang II affects Plasmodium growth and disease outcome in vivo, the P. berghei-ANKA infection of C57BL/6 mice model of malaria was used
Summary
Malaria is still a major public health problem world wide, causing more than 200 million cases per year and approximately 600,000 deaths, mostly in African children [1]. Of those that die from malaria, a high proportion succumb to cerebral malaria, a syndrome characterized by impaired consciousness, generalized convulsions, coma and neurological sequelae [2]. The interaction between Plasmodium falciparum infected red blood cells and host endothelial cells plays a key role in cerebral malaria. Mature stage parasites express ligands (PfEMP1) on the PLOS ONE | DOI:10.1371/journal.pone.0138191. Angiotensin II Inhibits Plasmodium Infection and Cerebral Malaria Mature stage parasites express ligands (PfEMP1) on the PLOS ONE | DOI:10.1371/journal.pone.0138191 September 16, 2015
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