Background. Clinical applications of HIV protease inhibitors for treatment of HIV infection have been associated with significant cardiovascular complications. The objective of this study was to determine the effects of HIV protease inhibitor ritonavir (RTV) on endothelial permeability and expression of junctional proteins as well as the effects of several antioxidants as potential therapeutic agents. Methods. Human coronary artery endothelial cells (HCAECs) were cultured with RTV (0, 7.5, 15, and 30 μM) for different times. Monolayer permeability was studied by using a transwell system and a fluorescence-labeled dextran trancer. The mRNA levels of endothelial junctional proteins including zonula occludens-1 (ZO-1), occludin, claudin-1, and VE-cadherin were quantitatively determined by real-time RT-PCR. Three antioxidants, curcumin (CUR), epigallocatechin gallate (EGCG), and seleno-L-methionine (SLM) at concentrations of 5, 10, and 25 μM, were used for blocking the effects of RTV. Results. RTV treatment showed a significant increase of monolayer permeability and a decrease of mRNA levels of four junctional proteins in a dose- and time-dependent fashion ( P < 0.03, n = 3). Three antioxidants showed a potent blocking effect on RVT (15 μM) in a dose-dependent fashion. Effects of RTV at 15 μM with or without one of antioxidants (25 μM) are shown in the table below. Conclusions. HIV protease inhibitor RTV significantly increases monolayer permeability and reduces expression of junctional proteins in HCAECs. Three antioxidants (CUR, EGCG, and SLM) can effectively block RTV-induced endothelial dysfunction and gene alterations. TABLE—ABSTRACT P47 Permeability ZO-1 Occludin Claudin-1 VE-cadherin Control 100% 100% 100% 100% 100% RTV 207% 76% 44% 15% 87% RTV + CUR 117% 71% 101% 43% 72% RTV + EGCG 139% 107% 101% 373% 107% RTV + SLM 138% 100% 101% 96% 100%