title: Physiologic changes in a nonhuman primate model of HIV-associated pulmonary arterial hypertension.
abstract: Pulmonary arterial hypertension (PAH) is increased in HIV, but its pathogenesis is not fully understood. Nonhuman primates infected with simian immunodeficiency virus (SIV) or SIV-HIV chimeric virus (SHIV) exhibit histologic changes characteristic of human PAH, but whether hemodynamic changes accompany this pathology is unknown. Repeated measurements of pulmonary artery pressures would permit longitudinal assessments of disease development and provide insights into pathogenesis. We tested the hypothesis that SIV-infected and SHIV-infected macaques develop physiologic manifestations of PAH. We performed right heart catheterizations, echocardiography, and computed tomography (CT) scans in macaques infected with either SIV (ΔB670) or SHIV (89.6P), and compared right heart and pulmonary artery pressures, as well as pulmonary vascular changes on CT scans, with those in uninfected control animals. Right atrial, right ventricular systolic, and pulmonary artery pressures (PAPs) were significantly elevated in 100% of macaques infected with either SIV or SHIV compared with control animals, with no difference in pulmonary capillary wedge pressure. PAPs increased as early as 3 months after SIV infection. Radiographic evidence of pulmonary vascular pruning was also found. Both SIV-infected and SHIV-infected macaques exhibited histologic changes in pulmonary arteries, predominantly consisting of intimal and medial hyperplasia. This report is the first to demonstrate SHIV-infected and SIV-infected macaques develop pulmonary hypertension at a high frequency, with physiologic changes occurring as early as 3 months after infection. These studies establish an important nonhuman primate model of HIV-associated PAH that will be useful in studies of disease pathogenesis and the efficacy of interventions.
authors.affiliation: Department of Immunology, School of Medicine, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15261. kan1@pitt.edu.edu.
authors.forename: M Patricia
authors.initials: MP
authors.lastname: George
authors.forename: Hunter C
authors.initials: HC
authors.lastname: Champion
authors.forename: Marc
authors.initials: M
authors.lastname: Simon
authors.forename: Siobhan
authors.initials: S
authors.lastname: Guyach
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tarantelli
authors.forename: Heather M
authors.initials: HM
authors.lastname: Kling
authors.forename: Alexandra
authors.initials: A
authors.lastname: Brower
authors.forename: Christopher
authors.initials: C
authors.lastname: Janssen
authors.forename: Jessica
authors.initials: J
authors.lastname: Murphy
authors.forename: Jonathan P
authors.initials: JP
authors.lastname: Carney
authors.forename: Alison
authors.initials: A
authors.lastname: Morris
authors.forename: Mark T
authors.initials: MT
authors.lastname: Gladwin
authors.forename: Karen A
authors.initials: KA
authors.lastname: Norris
mesh_terms: D000818:Animals; D062186:Arterial Pressure / Q000502:physiology; D004195:Disease Models, Animal; D065627:Familial Primary Pulmonary Hypertension; D006678:HIV; D015658:HIV Infections / Q000503:physiopathology* / Q000821:virology; D006352:Heart Ventricles / Q000503:physiopathology; D006801:Humans; D006976:Hypertension, Pulmonary / Q000503:physiopathology / Q000821:virology*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D011651:Pulmonary Artery / Q000503:physiopathology; D016097:Simian Acquired Immunodeficiency Syndrome / Q000503:physiopathology*; D015302:Simian Immunodeficiency Virus