Document Detail


Physiologic changes in a nonhuman primate model of HIV-associated pulmonary arterial hypertension.
MedLine Citation:
PMID:  23239493     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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:
M Patricia George; Hunter C Champion; Marc Simon; Siobhan Guyach; Rebecca Tarantelli; Heather M Kling; Alexandra Brower; Christopher Janssen; Jessica Murphy; Jonathan P Carney; Alison Morris; Mark T Gladwin; Karen A Norris
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-12-13
Journal Detail:
Title:  American journal of respiratory cell and molecular biology     Volume:  48     ISSN:  1535-4989     ISO Abbreviation:  Am. J. Respir. Cell Mol. Biol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-03-04     Completed Date:  2013-07-15     Revised Date:  2014-04-17    
Medline Journal Info:
Nlm Unique ID:  8917225     Medline TA:  Am J Respir Cell Mol Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  374-81     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Arterial Pressure / physiology
Disease Models, Animal*
HIV*
HIV Infections / physiopathology*,  virology
Heart Ventricles / physiopathology
Humans
Hypertension, Pulmonary / physiopathology,  virology*
Macaca fascicularis
Macaca mulatta
Pulmonary Artery / physiopathology
Simian Acquired Immunodeficiency Syndrome / physiopathology*
Simian immunodeficiency virus*
Grant Support
ID/Acronym/Agency:
3UL1RR024153-04S3/RR/NCRR NIH HHS; 5R01 HL077095/HL/NHLBI NIH HHS; P01 HL103455/HL/NHLBI NIH HHS; R01 HL083462/HL/NHLBI NIH HHS; UL1 TR000005/TR/NCATS NIH HHS
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