Antiretrovirals induce endothelial dysfunction via an oxidant-dependent pathway and promote neointimal hyperplasia

Toxicological Sciences

Volumn 117, Issue 2, 2010, Pages 524-536

  Jiang, Bo ^a   Khandelwal, Alok R ^a   Rogers, Lynette K ^b   Hebert, Valeria Y ^a   Kleinedler, James J ^a   Zavecz, James H ^a   Shi, Weibin ^c   Orr, A Wayne ^d   Dugas, Tammy R ^a  

^a LOUISIANA STATE UNIVERSITY HEALTH SCIENCES CENTER   (United States)

^b THE RESEARCH INSTITUTE AT NATIONWIDE CHILDREN S HOSPITAL   (United States)

^c UNIVERSITY OF VIRGINIA   (United States)

^d Louisiana State University School of Medicine Shreveport   (United States)

Author keywords

Antiretrovirals; Atherosclerosis; Endothelial dysfunction; Neointimal hyperplasia; Oxidative stress

Indexed keywords

ACONITATE HYDRATASE; ANTIOXIDANT; CHOLESTEROL; DIMETHYLARGININASE; INDINAVIR; MANGANESE TETRAKIS 1 METHYL 4 PYRIDYLPORPHYRIN; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; VASCULAR CELL ADHESION MOLECULE 1; ZIDOVUDINE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIOXIDANT ACTIVITY; ARTERY INTIMA PROLIFERATION; ARTICLE; CELL PROLIFERATION; CHOLESTEROL BLOOD LEVEL; CONTROLLED STUDY; DISEASE EXACERBATION; ENDOTHELIAL DYSFUNCTION; EPITHELIZATION; HIGHLY ACTIVE ANTIRETROVIRAL THERAPY; LIPID BLOOD LEVEL; MALE; MOUSE; NONHUMAN; SMOOTH MUSCLE FIBER; TREATMENT DURATION; TRIACYLGLYCEROL BLOOD LEVEL;

ANIMALS; ANTI-HIV AGENTS; ARGININE; ATHEROSCLEROSIS; BIOLOGICAL MARKERS; CELL PROLIFERATION; DRUG THERAPY, COMBINATION; ENDOTHELIUM, VASCULAR; FREE RADICAL SCAVENGERS; HYPERPLASIA; INDINAVIR; MALE; METALLOPORPHYRINS; MICE; MICE, INBRED C57BL; NEOINTIMA; ZIDOVUDINE;

ANIMALIA; HUMAN IMMUNODEFICIENCY VIRUS 1; MUS;

EID: 77956921021     PISSN: 10966080     EISSN: 10960929     Source Type: Journal    
DOI: 10.1093/toxsci/kfq213     Document Type: Article

References (51)

1. Barbaro, G., Di Lorenzo, G., Cirelli, A., Grisorio, B., Lucchini, A., Hazra, C., and Barbarini, G. (2003). An open-label, prospective, observational study of the incidence of coronary artery disease in patients with HIV infection receiving highly active antiretroviral therapy. Clin. Ther. 25, 2405-2418.
2. Berger, E. A., Murphy, P. M., and Farber, J. M. (1999). Chemokine receptors as HIV-1 coreceptors: roles in viral entry, tropism, and disease. Annu. Rev. Immunol. 17, 657-700.
3. Bogaards, J. J., Bertrand, M., Jackson, P., Oudshoorn, M. J., Weaver, R. J., van Bladeren, P. J., and Walther, B. (2000). Determining the best animal model for human cytochrome P450 activities: a comparison of mouse, rat, rabbit, dog, micropig, monkey and man. Xenobiotica 30, 1131-1152.
4. Boger, R. H. (2005). Asymmetric dimethylarginine (ADMA) and cardiovascular disease: insights from prospective clinical trials. Vasc. Med. 10(Suppl. 1), S19-S25.
5. Boger, R. H., Sydow, K., Borlak, J., Thum, T., Lenzen, H., Schubert, B., Tsikas, D., and Bode-Boger, S. M. (2000). LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases. Circ. Res. 87, 99-105.
6. Caldwell, J. (1981). The current status of attempts to predict species differences in drug metabolism. Drug Metab. Rev. 12, 221-237.
7. Chai, H., Yang, H., Yan, S., Li, M., Lin, P. H., Lumsden, A. B., Yao, Q., and Chen, C. (2005a). Effects of 5 HIV protease inhibitors on vasomotor function and superoxide anion production in porcine coronary arteries. J. Acquir. Immune Defic. Syndr. 40, 12-19.
8. Chai, H., Zhou, W., Lin, P., Lumsden, A., Yao, Q., and Chen, C. (2005b). Ginsenosides block HIV protease inhibitor ritonavir-induced vascular dysfunction of porcine coronary arteries. Am. J. Physiol. Heart Circ. Physiol. 288, H2965-H2971.
9. Charakida, M., Donald, A. E., Green, H., Storry, C., Clapson, M., Caslake, M., Dunn, D. T., Halcox, J. P., Gibb, D. M., Klein, N. J., et al. (2005). Early structural and functional changes of the vasculature in HIV-infected children: impact of disease and antiretroviral therapy. Circulation 112, 103-109.
10. Chi, D., Henry, J., Kelley, J., Thorpe, R., Smith, J. K., and Krishnaswamy, G. (2000). The effects of HIV infection on endothelial function. Endothelium 7, 223-242.
11. Cooke, J. P. (2000). Does ADMA cause endothelial dysfunction? Arterioscler. Thromb. Vasc. Biol. 20, 2032-2037.
12. Day, B. J., Fridovich, I., and Crapo, J. D. (1997). Manganic porphyrins possess catalase activity and protect endothelial cells against hydrogen peroxidemediated injury. Arch. Biochem. Biophys. 347, 256-262.
13. de Gaetano Donati, K., Rabagliati, R., Tumbarello, M., Tacconelli, E., Amore, C., Cauda, R., and Lacoviello, L. (2003). Increased soluble markers of endothelial dysfunction in HIV-positive patients under highly active antiretroviral therapy. Aids 17, 765-768.
14. Dube, M. P., Gorski, J. C., and Shen, C. (2008). Severe impairment of endothelial function with the HIV-1 protease inhibitor indinavir is not mediated by insulin resistance in healthy subjects. Cardiovasc. Toxicol. 8, 15-22.
15. Faulkner, K. M., Liochev, S. I., and Fridovich, I. (1994). Stable Mn(III) porphyrins mimic superoxide dismutase in vitro and substitute for it in vivo. J. Biol. Chem. 269, 23471-23476.
16. Friis-Moller, N., Sabin, C. A., Weber, R., d'Arminio Monforte, A., El-Sadr, W. M., Reiss, P., Thiebaut, R., Morfeldt, L., De Wit, S., Pradier, C., et al. (2003). Combination antiretroviral therapy and the risk of myocardial infarction. N. Engl. J. Med. 349, 1993-2003.
17. Gardner, P. R. (2002). Aconitase: sensitive target and measure of superoxide. Methods Enzymol. 349, 9-23.
18. Gottipolu, R. R., Wallenborn, J. G., Karoly, E. D., Schladweiller, M. C., Ledbetter, A. D., Krantz, T., Linak, W. P., Nyska, A., Johnson, J. A., and Thomas, R. (2009). One-month diesel exhaust inhalation produces hypertensive gene expression pattern in healthy rats. Environ. Health Perspect. 117, 38-46.
19. Hebert, V. Y., Crenshaw, B. L., Romanoff, R. L., Ekshyyan, V. P., and Dugas, T. R. (2004). Effects of HIV drug combinations on endothelin-1 and vascular cell proliferation. Cardiovasc. Toxicol. 4, 117-131.
20. Heresztyn, T., Worthley, M. I., and Horowitz, J. D. (2004). Determination of l-arginine and NG, NG - and NG, NG' -dimethyl-L-arginine in plasma by liquid chromatography as AccQ-Fluor fluorescent derivatives. J. Chromatogr. B Analyt. Technol. Biomed. Life. Sci. 805, 325-329.
21. Holme, P. A., Muller, F., Solum, N. O., Brosstad, F., Froland, S. S., and Aukrust, P. (1998). Enhanced activation of platelets with abnormal release of RANTES in human immunodeficiency virus type 1 infection. FASEB J. 12, 79-89.
22. Jagadeesha, D. K., Miller, F. J., Jr., and Bhalla, R. C. (2009). Inhibition of apoptotic signaling and neointimal hyperplasia by tempol and nitric oxide synthase following vascular injury. J. Vasc. Res. 46, 109-118.
23. Jiang, B., Hebert, V. Y., Khandelwal, A. R., Stokes, K. Y., and Dugas, T. R. (2009). HIV-1 antiretrovirals induce oxidant injury and increase intimamedia thickness in an atherogenic mouse model. Toxicol. Lett. 187, 164-171.
24. Jiang, B., Hebert, V. Y., Li, Y., Mathis, J. M., Alexander, J. S., and Dugas, T. R. (2007). HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis. Toxicol. Appl. Pharmacol. 224, 60-71.
25. Jiang, B., Hebert, V. Y., Zavecz, J. H., and Dugas, T. R. (2006). Antiretrovirals induce direct endothelial dysfunction in vivo. J. Acquir. Immune Defic. Syndr. 42, 391-395.
26. 2-induced transferrin receptor-dependent apoptosis in endothelial cells: role of ubiquitin-proteasome pathway. Proc. Natl. Acad. Sci U.S.A. 100, 10653-10658.
27. Krejcy, K., Schwarzacher, S., Ferber, W., Plesch, C., Cybulsky, M. I., and Weidinger, F. F. (1996). Expression of VCAM-1 in rabbit iliac arteries is associated with vasodilator dysfunction of regenerated endothelium following balloon injury. Atherosclerosis 122, 59-67.
28. Lee, G. A., Rao, M. N., and Grunfeld, C. (2004). The effects of HIV protease inhibitors on carbohydrate and lipid metabolism. Curr. Infect. Dis. Rep. 6, 471-482.
29. Lin, J. H., Chiba, M., Balani, S. K., Chen, I. W., Kwie, G. Y., Vastag, K. J., and Nishime, J. A. (1996). Species differences in the pharmacokinetics and metabolism of indinavir, a potent human immunodeficiency virus protease inhibitor. J. Pharmacol. Exp. Ther. 24, 1111-1120.
30. Lorenz, M. W., Stephan, C., Harmjanz, A., Staszewski, S., Buehler, A., Bickel, M., von Kegler, S., Ruhkamp, D., Steinmetz, H., and Sitzer, M. (2008). Both long-term HIV infection and highly active antiretroviral therapy are independent risk factors for early carotid atherosclerosis. Atherosclerosis 196, 720-726.
31. Matzen, K., Dirkx, A. E., oude Egbrink, M. G., Speth, C., Gotte, M., Ascherl, G., Grimm, T., Griffioen, A. W., and Sturzl, M. (2004). HIV-1 Tat increases the adhesion of monocytes and T-cells to the endothelium in vitro and in vivo: implications for AIDS-associated vasculopathy. Virus Res. 104, 145-155.
32. Note, R., Maisonneuve, C., Letteron, P., Peytavin, G., Djouadi, F., Igoudjil, A., Guimont, M. C., Biour, M., Pessayre, D., and Fromenty, B. (2003). Mitochondrial and metabolic effects of nucleoside reverse transcriptase inhibitors (NRTIs) in mice receiving one of five single- and three dual-NRTI treatments. Antimicrob. Agents Chemother. 47, 3384-3392.
33. Papparella, I., Ceolotto, G., Berto, L., Cavalli, M., Bova, S., Cargnelli, G., Ruga, E., Milanesi, O., Franco, L., Mazzoni, M., et al. (2007). Vitamin C prevents zidovudine-induced NADPH oxidase activation and hypertension in the rat. Cardiovasc. Res. 72, 432-438.
34. Peng, S. X., Rockafellow, B. A., Skedzielewski, T. M., Huebert, N. D., and Hageman, W. (2009). Improved pharmacokinetic and bioavailability support of drug discovery using serial blood sampling in mice. J. Pharm. Sci. 98, 1877-1884.
35. Quijano, C., Castro, L., Peluffo, G., Valez, V., and Radi, R. (2007). Enhanced mitochondrial superoxide in hyperglycemic endothelial cells: direct measurements and formation of hydrogen peroxide and peroxynitrite. Am. J. Physiol. Heart Circ. Physiol 293, H3404-H3414.
36. Ruifrok, A. C., and Johnston, D. A. (2001). Quantification of histochemical staining by color deconvolution. Anal. Quant. Cytol. Histol. 23, 291-299.
37. Sabin, C. A., Worm, S. W., Weber, R., Reiss, P., El-Sadr, W., Dabis, F., De Wit, S., Law, M., D'Arminio Monforte, A., Friis-Moller, N., et al. (2008). Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the DAD study: a multi-cohort collaboration. Lancet 371, 1417-1426.
38. Sankatsing, R. R., Wit, F. W., Vogel, M., de Groot, E., Brinkman, K., Rockstroh, J. K., Kastelein, J. J., Stroes, E. S., and Reiss, P. (2009). Increased carotid intima-media thickness in HIV patients treated with protease inhibitors as compared to non-nucleoside reverse transcriptase inhibitors. Atherosclerosis 202, 589-595.
39. Santos, C. X., Tanaka, L. Y., Wosniak, J., Jr., and Laurindo, F. R. (2009). Mechanisms and implications of reactive oxygen species generation during the unfolded protein response: roles of endoplasmic reticulum oxidoreductases, mitochondrial electron transport, and NADPH oxidase. Antiox. Redox Signal. 11, 2409-2427.
40. Shankar, S. S., Dube, M. P., Gorski, J. C., Klaunig, J. E., and Steinberg, H. O. (2005). Indinavir impairs endothelial function in healthy HIV-negative men. Am. Heart J. 150, 933.
41. Shi, W., Pei, H., Fischer, J. J., James, J. C., Angle, J. F., Matsumoto, A. H., Helm, G. A., and Sarembock, I. J. (2004). Neointimal formation in two apolipoprotein E-deficient mouse strains with different atherosclerosis susceptibility. J. Lipid Res. 45, 2008-2014.
42. Soriano, V., Puoti, M., Peters, M., Benhamou, Y., Sulkowski, M., Zoulim, F., Mauss, S., and Rockstroh, J. (2008). Care of HIV patients with chronic hepatitis B: updated recommendations from the HIV-Hepatitis B Virus International Panel. AIDS 22, 1399-1410.
43. Stein, J. H., Klein, M. A., Bellehumeur, J. L., McBride, P. E., Wiebe, D. A., Otvos, J. D., and Sosman, J. M. (2001). Use of human immunodeficiency virus-1 protease inhibitors is associated with atherogenic lipoprotein changes and endothelial dysfunction. Circulation 104, 257-262.
44. Surdacki, A. (2008). L-arginine analogs-inactive markers or active agents in atherogenesis? Cardiovasc. Hematol. Agents Med. Chem. 6, 302-311.
45. Sutliff, R. L., Dikalov, S., Weiss, D., Parker, J., Raidel, S., Racine, A. K., Russ, R., Haase, C. P., Taylor, W. R., and Lewis, W. (2002). Nucleoside reverse transcriptase inhibitors impair endothelium-dependent relaxation by increasing superoxide. Am. J. Physiol. Heart Circ. Physiol. 283, H2363-H2370.
46. Szocs, K., Lassegue, B., Sorescu, D., Hilenski, L. L., Valppu, L., Couse, T. L., Wilcox, J. N., Quinn, M. T., Lambeth, J. D., and Griendling, K. K. (2002). Upregulation of Nox-based NADPH oxidases in restenosis after carotid injury. Arterioscler. Thromb. Vasc. Biol. 22, 21-27.
47. Vaughn, G., and Detels, R. (2007). Protease inhibitors and cardiovascular disease: analysis of the Los Angeles County adult spectrum of disease cohort. AIDS Care 19, 492-499.
48. Wu, C. C., Wen, S. C., Yang, C. W., Pu, S. Y., Tsai, K. C., and Chen, J. W. (2009). Plasma ADMA predicts restenosis of arteriovenous fistula. J. Am. Soc. Nephrol. 20, 213-222.
49. Zhang, W. Z., and Kaye, D. M. (2004). Simultaneous determination of arginine and seven metabolites in plasma by reversed-phase liquid chromatography with a time-controlled ortho-phthaldialdehyde precolumn derivatization. Anal. Biochem. 326, 87-92.
50. Zhou, H., Pandak, W. M., Jr., Lyall, V., Natarajan, R., and Hylemon, P. B. (2005). HIV protease inhibitors activate the unfolded protein response in macrophages: implication for atherosclerosis and cardiovascular disease. Mol. Pharmacol. 68, 690-700.
51. Zhu, B., Kuhel, D. G., Witte, D. P., and Hui, D. Y. (2000). Apolipoprotein E inhibits neointimal hyperplasia after arterial injury in mice. Am. J. Pathol. 157, 1839-1848.