HAART Drugs Induce Mitochondrial Damage and Intercellular Gaps and gp120 Causes Apoptosis

Abstract

HIV-1 infection is associated with serious cardiovascular complications, but the roles of HIV-1, viral proteins, and highly active antiretroviral therapy (HAART) drugs are not understood. HAART decreases the overall risk of heart disease but leads to metabolic disturbances and possibly coronary artery disease. We investigated toxicities of HIV-1, HIV-1 glycoprotein 120 (gp120), and HAART drugs for human coronary artery endothelial cells (CAECs), brain microvascular endothelial cells, and neonatal rat ventricular myocytes (NRVMs). HIV-1 and gp120, but not azidothymidine (AZT), induced apoptosis of NRVMs and CAECs. Ethylisothiourea, an inhibitor of nitric oxide synthase, inhibited apoptosis induction by gp120. AZT, HIV-1, and gp120 all damaged mitochondria of cardiomyocytes. HAART drugs, AZT, and indinavir, but not HIV-1, produced intercellular gaps between confluent endothelial cells and decreased transendothelial electrical resistance. In conclusion, HIV-1 and gp120 induce toxicity through induction of cardiomyocyte and endothelial cell apoptosis. HAART drugs disrupt endothelial cell junctions and mitochondria and could cause vascular damage.

Roles and Mechanisms of Human Immunodeficiency Virus Protease Inhibitor Ritonavir and Other Anti-Human Immunodeficiency Virus Drugs in Endothelial Dysfunction of Porcine Pulmonary Arteries and Human Pulmonary Artery Endothelial Cells

“…31 HAART drugs AZT and indinavir disrupt endothelial cell junctions and mitochondria and cause vascular damage. 32 The recent studies from our laboratory demonstrated that the superoxide anion levels were significantly increased in porcine coronary arteries treated with ritonavir and amprenavir. 33,34 New findings in the current study further demonstrate the role of ROS system in HAART drug-treated porcine pulmonary arteries and HPAECs.…”

Cardiovascular complications in the acquired immunodeficiency syndrome

“…and PI disrupt endothelial cell junctions and cytoskeleton action of the endothelial cells leading to endothelial dysfunction 70 . These findings are in agreement with those previously reported in vivo by Stein et al 71 and in vitro by Zhong et al 72 .…”

197. Highly Active Antiretroviral Therapy Drugs Inhibit In Vitro Cholesterol Efflux from Human Macrophage-Derived Foam Cells

“…Mondal et al provided evidence that exposure of either IDV or nelfinavir combined with zidovudine and efavirenz increased ROS formation in human aortic endothelial cells.24 HAART drugs zidovudine and IDV disrupt endothelial cell junctions and mitochondria and could cause vascular damage. 25 The current data provide further understanding of the role of HAART 3-plex in the ROS system of THP-1-derived foam cells, indicating that the oxidative stress may be directly involved in the inhibition in cholesterol efflux induced by HAART drugs. Thus, antioxidant may have the potential to prevent the damage induced by HAART drugs in the vascular system..…”