*8.4. Malaria*

Malaria is a parasitic disease caused by *Plasmodium* infection, transmitted to humans through the bite of infected female *Anopheles* mosquitoes [265]. Cerebral malaria is a severe complication, occurring in approximately 1% of those infected, and is the main cause of death [266]. The role of ABCA1 in microvesicle formation seems to be relevant in the pathogenesis of cerebral malaria. *Abca1* KO mice showed lower plasma concentrations of microvesicles, and when infected with *Plasmodium berghei ANKA*, these mice show complete resistance to cerebral malaria. In addition, plasma tumor necrosis factor alpha concentrations were reduced, decreasing the proinflammatory and prothrombotic state [212]. Furthermore, *ABCA1* promoter variants were associated with increased microvesicle production and a higher risk of developing severe malaria in humans, suggesting that *ABCA1* genetic variation may confer susceptibility to the development of malaria and its complications [215]. Because miR-27a was found to inhibit *ABCA1* expression in vitro, to abolish microvesicle production and inhibit apoptotic mechanisms, this miRNA has been proposed as protective against cerebral malaria [267,268]. Interestingly, in a murine model of malaria

infection during pregnancy, *Abca1* expression was increased in the endothelial cells of the yolk sac. This event may be the result of a compensatory mechanism to maintain cholesterol homeostasis and favor the development and survival of the fetus [269]. Thus, ABCA1 may have a dual role, sometimes favoring infection and sometimes conferring protection.

Further research is required to fully elucidate how ABCA1 and cholesterol homeostasis are involved in infections, and to establish whether ABCA1 can in fact be a therapeutic target.
