title: The High Blood Pressure-Malaria Protection Hypothesis.
abstract: BACKGROUND
  A recently proposed hypothesis states that malaria may contribute to hypertension in endemic areas,1but the role of angiotensin II (Ang II), a major regulator of blood pressure, was not considered. Elevated levels of Ang II may confer protection against malaria morbidity and mortality, providing an alternative explanation for hypertension in malaria endemic areas.
  
  
  OBJECTIVE
  To discuss a possible alternative cause for hypertension in populations who have been under the selective pressure of malaria.
  
  
  RESULTS
  We reviewed published scientific literature for studies that could establish a link between Ang II and malaria. Both genetic and functional studies suggested that high levels of Ang II may confer protection against cerebral malaria by strengthening the integrity of the endothelial brain barrier. We also describe strong experimental evidence supporting our hypothesis through genetic, functional, and interventional studies.
  
  
  CONCLUSIONS
  A causal association between high levels of Ang II and protection from malaria pathogenesis can provide a likely explanation for the increased prevalence in hypertension observed in populations of African and South Asian origin. Furthermore, this potential causative connection might also direct unique approaches for the effective treatment of cerebral malaria.
authors.affiliation: From the Department of Microbiology, New York University School of Medicine (J.G.-D., A.R.); and Department of Pharmacology and Therapeutics, School of Medicine and School of Pharmacy, University College Cork (UCC), Ireland (T.W.).
authors.forename: Julio
authors.initials: J
authors.lastname: Gallego-Delgado
authors.affiliation: From the Department of Microbiology, New York University School of Medicine (J.G.-D., A.R.); and Department of Pharmacology and Therapeutics, School of Medicine and School of Pharmacy, University College Cork (UCC), Ireland (T.W.). t.walther@ucc.ie.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walther
authors.affiliation: From the Department of Microbiology, New York University School of Medicine (J.G.-D., A.R.); and Department of Pharmacology and Therapeutics, School of Medicine and School of Pharmacy, University College Cork (UCC), Ireland (T.W.).
authors.forename: Ana
authors.initials: A
authors.lastname: Rodriguez
mesh_terms: D000349:Africa / Q000453:epidemiology; D000804:Angiotensin II / Q000502:physiology*; D047228:Angiotensin II Type 1 Receptor Blockers / Q000627:therapeutic use; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001208:Asia / Q000453:epidemiology; D015984:Causality; D060467:Disease Resistance / Q000235:genetics; D004353:Drug Evaluation, Preclinical; D019353:Endemic Diseases; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D006973:Hypertension / Q000208:ethnology / Q000209:etiology* / Q000235:genetics; D016779:Malaria, Cerebral / Q000188:drug therapy* / Q000503:physiopathology; D016778:Malaria, Falciparum / Q000150:complications* / Q000208:ethnology / Q000235:genetics; D051379:Mice; D008954:Models, Biological; D007703:Peptidyl-Dipeptidase A / Q000235:genetics*; D011110:Polymorphism, Genetic; D015995:Prevalence; D044139:Receptor, Angiotensin, Type 2 / Q000819:agonists; D012641:Selection, Genetic
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2
keywords: angiotensin II; blood pressure; epidemiology; hypertension; malaria