A dual hit of HIV-1 plus IVDU on Pulmonary vascular remodeling

International Conference and Exhibition on Lung Disorders & Therapeutics

July 13-15, 2015 Baltimore, Maryland, USA

Navneet K Dhillon

Posters-Accepted Abstracts: J Pulm Respir Med

Abstract :

Intravenous Drug Use (IVDU) has been found to be one of the major risk factors for HIV-infection in the HIV Related Pulmonary Arterial Hypertension (HRPAH) patients. Our previous findings showing enhanced pulmonary vascular remodeling in HIVinfected lung tissues from IV heroin and/or cocaine abusers indicates that IVDU and HIV-1 potentially act in concert to cause pulmonary arteriopathy. Our study of lung tissues from simian immunodeficiency virus (SIV)-infected morphine treated macaques (VM) demonstrated significant pulmonary vascular remodeling when compared with either the SIV-infected or un-infected morphine treated groups. Furthermore, the endothelial cells (ECs) lining the vessels showing medial hypertrophy or initial stage intimal lesions in lung sections from VM macaques demonstrated an increase in positivity for both TUNEL and Ki67. This observation was supported by cell culture studies demonstrating enhanced apoptosis followed by enhanced proliferation of apoptotic resistant endothelial cells upon simultaneous treatment with HIV-Tat and morphine compared to either treatment alone. However, what causes the polarization of endothelial cells from apoptosis to apoptosis resistant hyper-proliferative state is not clear. In light of the emerging realization of cross talk between autophagy and apoptosis is controlling the cell death and cell-survival, we examined autophagy in ECs exposed to Tat and morphine. Our findings indicate that morphine in combination with viral protein(s) results in the synergistic induction of autophagy of pulmonary ECs that may be involved in switching of apoptotic cells to apoptosis resistant proliferative ECs. This may have led to the increase in the severity of angio-proliferative remodeling of the pulmonary vasculature that was observed on SIV/HIV-infection in the presence of opioids.