Human Immunodeficiency Virus‐1 Transgene Expression Increases Pulmonary Vascular Resistance and Exacerbates Hypoxia‐Induced Pulmonary Hypertension Development. (1st January 2013)

• Record Type: Journal Article
• Authors: Porter, Kristi M.; Walp, Erik R.; Elms, Shawn C.; Raynor, Robert; Mitchell, Patrick O.; Guidot, David M.; Sutliff, Roy L.
• Is Part Of: Pulmonary circulation. Volume 3:Number 1(2013)
• Page Start: 58
• Page End: 67
• Publication Date: 2013-01-01
• Subjects: human immunodeficiency virus -- chronic hypoxia -- pulmonary hypertension; Pulmonary circulation -- Periodicals; Pulmonary circulation; Electronic journals -- Sciences; Periodicals; 616.24005
• DOI: 10.4103/2045-8932.109915
• Languages: English
• ISSNs: 2045-8932

Abstract

Abstract : Pulmonary arterial hypertension (PAH) is a progressive disease characterized by increased pulmonary arterial resistance and vessel remodeling. Patients living with human immunodeficiency virus‐1 (HIV‐1) have an increased susceptibility to develop severe pulmonary hypertension (PH) irrespective of their CD4+ lymphocyte counts. While the underlying cause of HIV‐PAH remains unknown, the interaction of HIV‐1 proteins with the vascular endothelium may play a critical role in HIV‐PAH development. Hypoxia promotes PH in experimental models and in humans, but the impact of HIV‐1 proteins on hypoxia‐induced pulmonary vascular dysfunction and PAH has not been examined. Therefore, we hypothesize that the presence of HIV‐1 proteins and hypoxia synergistically augment the development of pulmonary vascular dysfunction and PH. We examined the effect of HIV‐1 proteins on pulmonary vascular resistance by measuring pressure‐volume relationships in isolated lungs from wild‐type (WT) and HIV‐1 Transgenic (Tg) rats. WT and HIV‐1 Tg rats were exposed to 10% O2 for four weeks to induce experimental pulmonary hypertension to assess whether HIV‐1 protein expression would impact the development of hypoxia‐induced PH. Our results demonstrate that HIV‐1 protein expression significantly increased pulmonary vascular resistance (PVR). HIV‐1 Tg mice demonstrated exaggerated pulmonary vascular responses to hypoxia as evidenced by greater increases in right ventricular systolic pressures, right ventricular hypertrophy and vessel muscularization when compared to wild‐type controls. This enhanced PH was associated with enhanced expression of HIF‐1α and PCNA. In addition, in vitro studies reveal that medium from HIV‐infected monocyte derived macrophages (MDM) potentiates hypoxia‐induced pulmonary artery endothelial proliferation. These results indicate that the presence of HIV‐1 proteins likely impact pulmonary vascular resistance and exacerbate hypoxia‐induced PH.