PATHOGENESIS OF PULMONARY ARTERIOPATHY IN SIMIAN AIDS

$377,899P51FY2011RRNIH

University Of Washington, Seattle WA

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Abstract

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. We have observed a syndrome in Macaca nemestrina infected with SIV or SHIV, consisting of pulmonary arteriopathy, thrombocytopenia, and potentially fatal thrombi in the right ventricle or pulmonary artery. Similar problems can occur in HIV-infected humans, although no clear relationship among the problems has been demonstrated. The mechanism and pathogenesis of this syndrome cannot be determined from the data currently available. The goal of this pilot project is to assess biomarkers and techniques which can be used in the future to investigate the pathogenesis of this syndrome in macaques, and determine the utility of this model in the investigation of HIV-related complications in humans. An experiment involving SHIV-infected animals reached completion, and we were able to assess the 23 remaining animals using echocardiography and a panel of coagulation biomarkers at three monthly timepoints. Techniques were standardized and normal ranges determined. Limited sample sets were collected from two animals that developed pulmonary arteriopathy and were euthanized prior to standardized assessment. These animals both displayed abnormalities of the heart and of coagulation parameters, suggesting that these parameters will be useful in future studies. Histopathology is underway to determine the relationship of these parameters to different stages in the development of arteriopathy.

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