Statin treatment prevents the development of pulmonary arterial hypertension in a nonhuman primate model of HIV-associated PAH

Sci Rep. 2019 Dec 27;9(1):19832. doi: 10.1038/s41598-019-55301-9.


Pulmonary arterial hypertension (PAH) is a life-threatening disease characterized by pulmonary vascular remodeling, elevated pulmonary arterial pressure, and right heart failure. Human immunodeficiency virus (HIV)-infected individuals have a higher incidence of PAH than the non-HIV infected population and evidence suggests a role for systemic and pulmonary inflammation in the pathogenesis of HIV-associated PAH. Due to their pleiotropic effects, including immune-modulatory and anti-inflammatory effects, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) have been considered for the treatment of PAH, with conflicting results. The effects of statins on HIV-associated PAH have not been specifically evaluated. We have developed a non-human primate (NHP) model of HIV-associated PAH that closely mimics HIV-PAH using simian immunodeficiency virus (SIV)-infected rhesus macaques (Macaca mulatta). We determined that treatment of healthy macaques with atorvastatin prior to and throughout SIV infection prevented the development of SIV-associated PAH. Additionally, SIV-infected macaques that initiated atorvastatin treatment during the early chronic disease stage had reduced incidence of PAH compared to untreated animals. Statin treatment reduced inflammatory mediators TGF-β, MIP-1α, and TNF-α and the numbers of CD14dimCD16+ non-classical monocytes, and CD14+CCR7-CD163-CD206+ alveolar macrophages previously shown to be associated with SIV-PAH. These results support the concept that statins reduce inflammatory processes that contribute to PAH and may provide a safe and effective prophylactic strategy for the prevention of PAH in HIV-infected individuals.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Atorvastatin / pharmacology
  • Disease Models, Animal
  • HIV / drug effects*
  • HIV / physiology
  • HIV Infections / complications*
  • HIV Infections / virology
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Macaca mulatta / virology
  • Macrophages, Alveolar / drug effects
  • Macrophages, Alveolar / virology
  • Monocytes / drug effects
  • Monocytes / virology
  • Pulmonary Arterial Hypertension / complications
  • Pulmonary Arterial Hypertension / prevention & control*
  • Simian Acquired Immunodeficiency Syndrome / complications
  • Simian Acquired Immunodeficiency Syndrome / virology
  • Simian Immunodeficiency Virus / drug effects
  • Simian Immunodeficiency Virus / physiology
  • Viral Load / drug effects


  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Atorvastatin