HIV-1–Associated Atherosclerosis: Unraveling the Missing Link

Journal of the American College of Cardiology

Volumn 69, Issue 25, 2017, Pages 3084-3098

  Kearns, Alison ^a   Gordon, Jennifer ^a   Burdo, Tricia H ^a   Qin, Xuebin ^a  

^a TEMPLE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

caspase 1; immune activation; inflammasome; inflammation; macrophage; Tg26 transgenic mice

Indexed keywords

ANTIRETROVIRUS AGENT; BIOLOGICAL MARKER; CRYOPYRIN; INFLAMMASOME; REACTIVE OXYGEN METABOLITE;

ANTIRETROVIRAL THERAPY; ATHEROSCLEROSIS; ATHEROSCLEROTIC PLAQUE; AUTOPHAGY; CARDIOVASCULAR DISEASE; CARDIOVASCULAR RISK; COMORBIDITY; ENDOPLASMIC RETICULUM STRESS; FOAM CELL; HIGH RISK PATIENT; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS 1 INFECTION; MACROPHAGE; NONHUMAN; OXIDATIVE STRESS; PATHOGENESIS; PRIORITY JOURNAL; REVIEW; RISK ASSESSMENT; SIMIAN ACQUIRED IMMUNODEFICIENCY SYNDROME; TRANSGENIC MOUSE; CELLULAR IMMUNITY; COMPLICATION; GLOBAL HEALTH; HUMAN IMMUNODEFICIENCY VIRUS 1; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; IMMUNOLOGY; MORBIDITY; RISK FACTOR; SURVIVAL RATE; TRENDS; VIROLOGY;

ATHEROSCLEROSIS; GLOBAL HEALTH; HIV INFECTIONS; HIV-1; HUMANS; IMMUNITY, CELLULAR; MORBIDITY; RISK FACTORS; SURVIVAL RATE;

EID: 85027490312     PISSN: 07351097     EISSN: 15583597     Source Type: Journal    
DOI: 10.1016/j.jacc.2017.05.012     Document Type: Review

References (135)

1. Shrestha, S., Irvin, M.R., Grunfeld, C., Arnett, D.K., HIV, inflammation, and calcium in atherosclerosis. Arterioscler Thromb Vasc Biol 34 (2014), 244–250.
2. Vachiat, A., McCutcheon, K., Tsabedze, N., Zachariah, D., Manga, P., HIV and ischemic heart disease. J Am Coll Cardiol 69 (2017), 73–82.
3. Gili, S., Grosso Marra, W., D'Ascenzo, F., et al. Comparative safety and efficacy of statins for primary prevention in human immunodeficiency virus-positive patients: a systematic review and meta-analysis. Eur Heart J 37 (2016), 3600–3609.
4. D'Ascenzo, F., Quadri, G., Cerrato, E., et al. A meta-analysis investigating incidence and features of stroke in HIV-infected patients in the highly active antiretroviral therapy era. J Cardiovasc Med (Hagerstown) 16 (2015), 839–843.
5. D'Ascenzo, F., Cerrato, E., Biondi-Zoccai, G., et al. Acute coronary syndromes in human immunodeficiency virus patients: a meta-analysis investigating adverse event rates and the role of antiretroviral therapy. Eur Heart J 33 (2012), 875–880.
6. Smith, C.J., Ryom, L., Weber, R., et al., for the D: A:D Study Group. Trends in underlying causes of death in people with HIV from 1999 to 2011 (D: A:D): a multicohort collaboration. Lancet 384 (2014), 241–248.
7. Triant, V.A., Lee, H., Hadigan, C., Grinspoon, S.K., Increased acute myocardial infarction rates and cardiovascular risk factors among patients with human immunodeficiency virus disease. J Clin Endocrinol Metab 92 (2007), 2506–2512.
8. Freiberg, M.S., Chang, C.C., Kuller, L.H., et al. HIV infection and the risk of acute myocardial infarction. JAMA Intern Med 173 (2013), 614–622.
9. Zanni, M.V., Schouten, J., Grinspoon, S.K., Reiss, P., Risk of coronary heart disease in patients with HIV infection. Nat Rev Cardiol 11 (2014), 728–741.
10. Siedner, M.J., START or SMART? Timing of antiretroviral therapy initiation and cardiovascular risk for people with human immunodeficiency virus infection. Open Forum Infect Dis, 3, 2016, ofw032.
11. Strategies for Management of Antiretroviral Therapy (SMART) Study Group. CD4+ count-guided interruption of antiretroviral treatment. N Engl J Med 355 (2006), 2283–2296.
12. INSIGHT START Study Group. Initiation of antiretroviral therapy in early asymptomatic HIV infection. N Engl J Med 373 (2015), 795–807.
13. Pereyra, F., Lo, J., Triant, V.A., et al. Increased coronary atherosclerosis and immune activation in HIV-1 elite controllers. AIDS 26 (2012), 2409–2412.
14. Hsue, P.Y., Hunt, P.W., Schnell, A., et al. Role of viral replication, antiretroviral therapy, and immunodeficiency in HIV-associated atherosclerosis. AIDS 23 (2009), 1059–1067.
15. D'Ascenzo, F., Cerrato, E., Calcagno, A., et al. High prevalence at computed coronary tomography of non-calcified plaques in asymptomatic HIV patients treated with HAART: a meta-analysis. Atherosclerosis 240 (2015), 197–204.
16. Lo, J., Abbara, S., Shturman, L., et al. Increased prevalence of subclinical coronary atherosclerosis detected by coronary computed tomography angiography in HIV-infected men. AIDS 24 (2010), 243–253.
17. Post, W.S., Budoff, M., Kingsley, L., et al. Associations between HIV infection and subclinical coronary atherosclerosis. Ann Intern Med 160 (2014), 458–467.
18. Zanni, M.V., Abbara, S., Lo, J., et al. Increased coronary atherosclerotic plaque vulnerability by coronary computed tomography angiography in HIV-infected men. AIDS 27 (2013), 1263–1272.
19. Fitch, K.V., Srinivasa, S., Abbara, S., et al. Noncalcified coronary atherosclerotic plaque and immune activation in HIV-infected women. J Infect Dis 208 (2013), 1737–1746.
20. Silverberg, M.J., Leyden, W.A., Xu, L., et al. Immunodeficiency and risk of myocardial infarction among HIV-positive individuals with access to care. J Acquir Immune Defic Syndr 65 (2014), 160–166.
21. Longenecker, C.T., Triant, V.A., Initiation of antiretroviral therapy at high CD4 cell counts: does it reduce the risk of cardiovascular disease?. Curr Opin HIV AIDS 9 (2014), 54–62.
22. Burdo, T.H., Lo, J., Abbara, S., et al. Soluble CD163, a novel marker of activated macrophages, is elevated and associated with noncalcified coronary plaque in HIV-infected patients. J Infect Dis 204 (2011), 1227–1236.
23. Subramanian, S., Tawakol, A., Burdo, T.H., et al. Arterial inflammation in patients with HIV. JAMA 308 (2012), 379–386.
24. Duprez, D.A., Neuhaus, J., Kuller, L.H., et al., for the INSIGHT SMART Study Group. Inflammation, coagulation and cardiovascular disease in HIV-infected individuals. PloS One, 7, 2012, e44454.
25. Hsu, D.C., Ma, Y.F., Hur, S., et al. Plasma IL-6 levels are independently associated with atherosclerosis and mortality in HIV-infected individuals on suppressive antiretroviral therapy. AIDS 30 (2016), 2065–2074.
26. Kuller, L.H., Tracy, R., Belloso, W., et al., for the INSIGHT SMART Study Group. Inflammatory and coagulation biomarkers and mortality in patients with HIV infection. PLoS Med, 5, 2008, e203.
27. Friis-Møller, N., Weber, R., Reiss, P., et al., for the DAD Study Group. Cardiovascular disease risk factors in HIV patients—association with antiretroviral therapy. Results from the DAD study. AIDS 17 (2003), 1179–1193.
28. Beltrán, L.M., Rubio-Navarro, A., Amaro-Villalobos, J.M., Egido, J., García-Puig, J., Moreno, J.A., Influence of immune activation and inflammatory response on cardiovascular risk associated with the human immunodeficiency virus. Vasc Health Risk Manag 11 (2015), 35–48.
29. Sosner, P., Wangermez, M., Chagneau-Derrode, C., Le Moal, G., Silvain, C., Atherosclerosis risk in HIV-infected patients: the influence of hepatitis C virus co-infection. Atherosclerosis 222 (2012), 274–277.
30. Shahbaz, S., Manicardi, M., Guaraldi, G., Raggi, P., Cardiovascular disease in human immunodeficiency virus infected patients: a true or perceived risk?. World J Cardiol 7 (2015), 633–644.
31. Crowe, S.M., Westhorpe, C.L., Mukhamedova, N., Jaworowski, A., Sviridov, D., Bukrinsky, M., The macrophage: the intersection between HIV infection and atherosclerosis. J Leukoc Biol 87 (2010), 589–598.
32. Klatt, N.R., Chomont, N., Douek, D.C., Deeks, S.G., Immune activation and HIV persistence: implications for curative approaches to HIV infection. Immunol Rev 254 (2013), 326–342.
33. Shah, A., Kumar, A., HIV-1 gp120-mediated mitochondrial dysfunction and HIV-associated neurological disorders. Neurotox Res 30 (2016), 135–137.
34. Ipp, H., Zemlin, A., The paradox of the immune response in HIV infection: when inflammation becomes harmful. Clin Chim Acta 416 (2013), 96–99.
35. Kelesidis, T., Kendall, M.A., Yang, O.O., Hodis, H.N., Currier, J.S., Biomarkers of microbial translocation and macrophage activation: association with progression of subclinical atherosclerosis in HIV-1 infection. J Infect Dis 206 (2012), 1558–1567.
36. Shaked, I., Hanna, D.B., Gleißner, C., et al. Macrophage inflammatory markers are associated with subclinical carotid artery disease in women with human immunodeficiency virus or hepatitis C virus infection. Arterioscler Thromb Vasc Biol 34 (2014), 1085–1092.
37. Siedner, M.J., Kim, J.H., Nakku, R.S., et al. Persistent immune activation and carotid atherosclerosis in HIV-infected Ugandans receiving antiretroviral therapy. J Infect Dis 213 (2016), 370–378.
38. Alcaide, M.L., Parmigiani, A., Pallikkuth, S., et al. Immune activation in HIV-infected aging women on antiretrovirals—implications for age-associated comorbidities: a cross-sectional pilot study. PloS One, 8, 2013, e63804.
39. Ford, E.S., Greenwald, J.H., Richterman, A.G., et al. Traditional risk factors and D-dimer predict incident cardiovascular disease events in chronic HIV infection. AIDS 24 (2010), 1509–1517.
40. Ross, A.C., Rizk, N., O'Riordan, M.A., et al. Relationship between inflammatory markers, endothelial activation markers, and carotid intima-media thickness in HIV-infected patients receiving antiretroviral therapy. Clin Infect Dis 49 (2009), 1119–1127.
41. Westhorpe, C.L., Maisa, A., Spelman, T., et al. Associations between surface markers on blood monocytes and carotid atherosclerosis in HIV-positive individuals. Immunol Cell Biol 92 (2014), 133–138.
42. Hamon, P., Loyher, P.L., Baudesson de Chanville, C., Licata, F., Combadière, C., Boissonnas, A., CX3CR1-dependent endothelial margination modulates Ly6Chigh monocyte systemic deployment upon inflammation in mice. Blood 129 (2017), 1296–1307.
43. lo monocytosis and almost abolishes atherosclerosis in hypercholesterolemic mice. Circulation 117 (2008), 1649–1657.
44. Chow, D.C., Kagihara, J.M., Zhang, G., et al. Non-classical monocytes predict progression of carotid artery bifurcation intima-media thickness in HIV-infected individuals on stable antiretroviral therapy. HIV Clin Trials 17 (2016), 114–122.
45. McKibben, R.A., Margolick, J.B., Grinspoon, S., et al. Elevated levels of monocyte activation markers are associated with subclinical atherosclerosis in men with and those without HIV infection. J Infect Dis 211 (2015), 1219–1228.
46. Zungsontiporn, N., Tello, R.R., Zhang, G., et al. Non-classical monocytes and monocyte chemoattractant protein-1 (MCP-1) correlate with coronary artery calcium progression in chronically HIV-1 infected adults on stable antiretroviral therapy. PloS One, 11, 2016, e0149143.
47. Barbour, J.D., Jalbert, E.C., Chow, D.C., et al. Reduced CD14 expression on classical monocytes and vascular endothelial adhesion markers independently associate with carotid artery intima media thickness in chronically HIV-1 infected adults on virologically suppressive anti-retroviral therapy. Atherosclerosis 232 (2014), 52–58.
48. Pushkarsky, T., Shilov, E., Kruglova, N., et al. Short communication: accumulation of neutral lipids in liver and aorta of Nef-transgenic mice. AIDS Res Hum Retroviruses 33 (2017), 57–60.
49. Bernard, M.A., Han, X., Inderbitzin, S., et al. HIV-derived ssRNA binds to TLR8 to induce inflammation-driven macrophage foam cell formation. PloS One, 9, 2014, e104039.
50. Karim, R., Mack, W.J., Kono, N., et al. T-cell activation, both pre- and post-HAART levels, correlates with carotid artery stiffness over 6.5 years among HIV-infected women in the WIHS. J Acquir Immune Defic Syndr 67 (2014), 349–356.
51. Kaplan, R.C., Sinclair, E., Landay, A.L., et al. T cell activation and senescence predict subclinical carotid artery disease in HIV-infected women. J Infect Dis 203 (2011), 452–463.
52. Grome, H.N., Barnett, L., Hagar, C.C., Harrison, D.G., Kalams, S.A., Koethe, J.R., Association of T cell and macrophage activation with arterial vascular health in HIV. AIDS Res Hum Retroviruses 33 (2017), 181–186.
53. D'Abramo, A., Zingaropoli, M.A., Oliva, A., et al. Immune activation, immunosenescence, and osteoprotegerin as markers of endothelial dysfunction in subclinical HIV-associated atherosclerosis. Mediators Inflamm, 2014, 2014, 192594.
54. Longenecker, C.T., Funderburg, N.T., Jiang, Y., et al. Markers of inflammation and CD8 T-cell activation, but not monocyte activation, are associated with subclinical carotid artery disease in HIV-infected individuals. HIV Med 14 (2013), 385–390.
55. Merlini, E., Luzi, K., Suardi, E., et al. T-cell phenotypes, apoptosis and inflammation in HIV+ patients on virologically effective cART with early atherosclerosis. PloS One, 7, 2012, e46073.
56. Guaraldi, G., Luzi, K., Bellistri, G.M., et al. CD8 T-cell activation is associated with lipodystrophy and visceral fat accumulation in antiretroviral therapy-treated virologically suppressed HIV-infected patients. J Acquir Immune Defic Syndr 64 (2013), 360–366.
57. Hansson, G.K., Robertson, A.K., Söderberg-Nauclér, C., Inflammation and atherosclerosis. Annu Rev Pathol 1 (2006), 297–329.
58. Tawakol, A., Ishai, A., Li, D., et al. Association of arterial and lymph node inflammation with distinct inflammatory pathways in human immunodeficiency virus infection. JAMA Cardiol 2 (2017), 163–171.
59. Zanni, M.V., Toribio, M., Robbins, G.K., et al. Effects of antiretroviral therapy on immune function and arterial inflammation in treatment-naive patients with human immunodeficiency virus infection. JAMA Cardiol 1 (2016), 474–480.
60. Ivanov, A.V., Valuev-Elliston, V.T., Ivanova, O.N., et al. Oxidative stress during HIV infection: mechanisms and consequences. Oxid Med Cell Longev, 2016, 2016, 8910396.
61. Forman, H.J., Davies, K.J., Ursini, F., How do nutritional antioxidants really work: nucleophilic tone and para-hormesis versus free radical scavenging in vivo. Free Radic Biol Med 66 (2014), 24–35.
62. Cross, A.R., Segal, A.W., The NADPH oxidase of professional phagocytes—prototype of the NOX electron transport chain systems. Biochim Biophys Acta 1657 (2004), 1–22.
63. Jagadeesha, D.K., Takapoo, M., Banfi, B., Bhalla, R.C., Miller, F.J. Jr., Nox1 transactivation of epidermal growth factor receptor promotes N-cadherin shedding and smooth muscle cell migration. Cardiovasc Res 93 (2012), 406–413.
64. Miller, A.A., De Silva, T.M., Judkins, C.P., Diep, H., Drummond, G.R., Sobey, C.G., Augmented superoxide production by Nox2-containing NADPH oxidase causes cerebral artery dysfunction during hypercholesterolemia. Stroke 41 (2010), 784–789.
65. Perrotta, I., Aquila, S., The role of oxidative stress and autophagy in atherosclerosis. Oxid Med Cell Longev, 2015, 2015, 130315.
66. Wanchu, A., Rana, S.V., Pallikkuth, S., Sachdeva, R.K., Short communication: oxidative stress in HIV-infected individuals: a cross-sectional study. AIDS Res Hum Retroviruses 25 (2009), 1307–1311.
67. Parra, S., Coll, B., Aragonés, G., et al. Nonconcordance between subclinical atherosclerosis and the calculated Framingham risk score in HIV-infected patients: relationships with serum markers of oxidation and inflammation. HIV Med 11 (2010), 225–231.
68. Watanabe, L.M., Barbosa Júnior, F., Jordão, A.A., Navarro, A.M., Influence of HIV infection and the use of antiretroviral therapy on selenium and selenomethionine concentrations and antioxidant protection. Nutrition 32 (2016), 1238–1242.
69. Parsons, M., Campa, A., Lai, S., et al. Effect of GSTM1-polymorphism on disease progression and oxidative stress in HIV infection: modulation by HIV/HCV co-infection and alcohol consumption. J AIDS Clin Res, 4, 2013, 10002337.
70. Duffy, P., Wang, X., Lin, P.H., Yao, Q., Chen, C., HIV Nef protein causes endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells. J Surg Res 156 (2009), 257–264.
71. Huang, X., Liang, H., Fan, X., Zhu, L., Shen, T., Liver damage in patients with HCV/HIV coinfection is linked to HIV-related oxidative stress. Oxid Med Cell Longev, 2016, 2016, 8142431.
72. Hulgan, T., Morrow, J., D'Aquila, R.T., et al. Oxidant stress is increased during treatment of human immunodeficiency virus infection. Clin Infect Dis 37 (2003), 1711–1717.
73. Scull, C.M., Tabas, I., Mechanisms of ER stress-induced apoptosis in atherosclerosis. Arterioscler Thromb Vasc Biol 31 (2011), 2792–2797.
74. Zhou, J., Lhoták, S., Hilditch, B.A., Austin, R.C., Activation of the unfolded protein response occurs at all stages of atherosclerotic lesion development in apolipoprotein E-deficient mice. Circulation 111 (2005), 1814–1821.
75. Civelek, M., Manduchi, E., Riley, R.J., Stoeckert, C.J. Jr., Davies, P.F., Chronic endoplasmic reticulum stress activates unfolded protein response in arterial endothelium in regions of susceptibility to atherosclerosis. Circ Res 105 (2009), 453–461.
76. Clarke, M.C., Figg, N., Maguire, J.J., et al. Apoptosis of vascular smooth muscle cells induces features of plaque vulnerability in atherosclerosis. Nat Med 12 (2006), 1075–1080.
77. Feng, B., Yao, P.M., Li, Y., et al. The endoplasmic reticulum is the site of cholesterol-induced cytotoxicity in macrophages. Nat Cell Biol 5 (2003), 781–792.
78. Dong, Y., Zhang, M., Wang, S., et al. Activation of AMP-activated protein kinase inhibits oxidized LDL-triggered endoplasmic reticulum stress in vivo. Diabetes 59 (2010), 1386–1396.
79. Erbay, E., Babaev, V.R., Mayers, J.R., et al. Reducing endoplasmic reticulum stress through a macrophage lipid chaperone alleviates atherosclerosis. Nat Med 15 (2009), 1383–1391.
80. Myoishi, M., Hao, H., Minamino, T., et al. Increased endoplasmic reticulum stress in atherosclerotic plaques associated with acute coronary syndrome. Circulation 116 (2007), 1226–1233.
81. Ma, R., Yang, L., Niu, F., Buch, S., HIV Tat-mediated induction of human brain microvascular endothelial cell apoptosis involves endoplasmic reticulum stress and mitochondrial dysfunction. Mol Neurobiol 53 (2016), 132–142.
82. Chen, L., Jarujaron, S., Wu, X., et al. HIV protease inhibitor lopinavir-induced TNF-α and IL-6 expression is coupled to the unfolded protein response and ERK signaling pathways in macrophages. Biochem Pharmacol 78 (2009), 70–77.
83. Zhang, X., Cao, R., Liu, R., et al. Reduction of the HIV protease inhibitor-induced ER stress and inflammatory response by raltegravir in macrophages. PloS One, 9, 2014, e90856.
84. Strowig, T., Henao-Mejia, J., Elinav, E., Flavell, R., Inflammasomes in health and disease. Nature 481 (2012), 278–286.
85. Guo, H., Gao, J., Taxman, D.J., Ting, J.P., Su, L., HIV-1 infection induces interleukin-1β production via TLR8 protein-dependent and NLRP3 inflammasome mechanisms in human monocytes. J Biol Chem 289 (2014), 21716–21726.
86. Guo, H., Callaway, J.B., Ting, J.P., Inflammasomes: mechanism of action, role in disease, and therapeutics. Nat Med 21 (2015), 677–687.
87. Cai, Y., Arikkath, J., Yang, L., Guo, M.L., Periyasamy, P., Buch, S., Interplay of endoplasmic reticulum stress and autophagy in neurodegenerative disorders. Autophagy 12 (2016), 225–244.
88. High patient groups. PloS One, 10, 2015, e0121011.
89. Hernandez, J.C., Latz, E., Urcuqui-Inchima, S., HIV-1 induces the first signal to activate the NLRP3 inflammasome in monocyte-derived macrophages. Intervirology 57 (2014), 36–42.
90. Doitsh, G., Galloway, N.L., Geng, X., et al. Cell death by pyroptosis drives CD4 T-cell depletion in HIV-1 infection. Nature 505 (2014), 509–514.
91. Ridker, P.M., From C-reactive protein to interleukin-6 to interleukin-1: moving upstream to identify novel targets for atheroprotection. Circ Res 118 (2016), 145–156.
92. Yearley, J.H., Xia, D., Pearson, C.B., Carville, A., Shannon, R.P., Mansfield, K.G., Interleukin-18 predicts atherosclerosis progression in SIV-infected and uninfected rhesus monkeys (Macaca mulatta) on a high-fat/high-cholesterol diet. Lab Invest 89 (2009), 657–667.
93. Deretic, V., Jiang, S., Dupont, N., Autophagy intersections with conventional and unconventional secretion in tissue development, remodeling and inflammation. Trends Cell Biol 22 (2012), 397–406.
94. Yang, Z., Klionsky, D.J., Mammalian autophagy: core molecular machinery and signaling regulation. Curr Opin Cell Biol 22 (2010), 124–131.
95. Shao, B.Z., Han, B.Z., Zeng, Y.X., Su, D.F., Liu, C., The roles of macrophage autophagy in atherosclerosis. Acta Pharmacol Sinica 37 (2016), 150–156.
96. Boya, P., Reggiori, F., Codogno, P., Emerging regulation and functions of autophagy. Nat Cell Biol 15 (2013), 713–720.
97. Kiffin, R., Bandyopadhyay, U., Cuervo, A.M., Oxidative stress and autophagy. Antiox Redox Signal 8 (2006), 152–162.
98. −/− mice. Sci Rep, 4, 2014, 5519.
99. Martinet, W., Schrijvers, D.M., Timmermans, J.P., Bult, H., Interactions between cell death induced by statins and 7-ketocholesterol in rabbit aorta smooth muscle cells. Br J Pharmacol 154 (2008), 1236–1246.
100. Schrijvers, D.M., De Meyer, G.R., Martinet, W., Autophagy in atherosclerosis: a potential drug target for plaque stabilization. Arterioscler Thromb Vasc Biol 31 (2011), 2787–2791.
101. Liao, X., Sluimer, J.C., Wang, Y., et al. Macrophage autophagy plays a protective role in advanced atherosclerosis. Cell Metab 15 (2012), 545–553.
102. Dinkins, C., Pilli, M., Kehrl, J.H., Roles of autophagy in HIV infection. Immunol Cell Biol 93 (2015), 11–17.
103. Blanchet, F.P., Moris, A., Nikolic, D.S., et al. Human immunodeficiency virus-1 inhibition of immunoamphisomes in dendritic cells impairs early innate and adaptive immune responses. Immunity 32 (2010), 654–669.
104. Kyei, G.B., Dinkins, C., Davis, A.S., et al. Autophagy pathway intersects with HIV-1 biosynthesis and regulates viral yields in macrophages. J Cell Biol 186 (2009), 255–268.
105. Guo, W., Wong, S., Pudney, J., et al. Acipimox, an inhibitor of lipolysis, attenuates atherogenesis in LDLR-null mice treated with HIV protease inhibitor ritonavir. Arterioscler Thromb Vasc Biol 29 (2009), 2028–2032.
106. Caulk, A.W., Soler, J., Platt, M.O., Gleason, R.L. Jr., Efavirenz treatment causes arterial stiffening in apolipoprotein E-null mice. J Biomech 48 (2015), 2176–2180.
107. Kopp, J.B., Klotman, M.E., Adler, S.H., et al. Progressive glomerulosclerosis and enhanced renal accumulation of basement membrane components in mice transgenic for human immunodeficiency virus type 1 genes. Proc Natl Acad Sci U S A 89 (1992), 1577–1581.
108. Raidel, S.M., Haase, C., Jansen, N.R., et al. Targeted myocardial transgenic expression of HIV Tat causes cardiomyopathy and mitochondrial damage. Am J Physiol Heart Circ Physiolo 282 (2002), H1672–H1678.
109. Fang, Q., Kan, H., Lewis, W., Chen, F., Sharma, P., Finkel, M.S., Dilated cardiomyopathy in transgenic mice expressing HIV Tat. Cardiovasc Toxicol 9 (2009), 39–45.
110. Pushkarsky, T., Shilov, E., Kruglova, N., et al. Accumulation of neutral lipids in liver and aorta of Nef-transgenic mice. AIDS Res Hum Retroviruses 33 (2017), 57–60.
111. Denton, P.W., Garcia, J.V., Novel humanized murine models for HIV research. Curr HIV/AIDS Rep 6 (2009), 13–19.
112. Curreli, S., Krishnan, S., Reitz, M., et al. B cell lymphoma in HIV transgenic mice. Retrovirology, 10, 2013, 92.
113. Haque, S., Lan, X., Wen, H., et al. HIV promotes NLRP3 inflammasome complex activation in murine HIV-associated nephropathy. Am J Pathol 186 (2016), 347–358.
114. Hansen, L., Parker, I., Sutliff, R.L., Platt, M.O., Gleason, R.L. Jr., Endothelial dysfunction, arterial stiffening, and intima-media thickening in large arteries from HIV-1 transgenic mice. Ann Biomed Eng 41 (2013), 682–693.
115. Mallipattu, S.K., Liu, R., Zhong, Y., et al. Expression of HIV transgene aggravates kidney injury in diabetic mice. Kidney Int 83 (2013), 626–634.
116. Kearns, A., Dai, S., Liu, F., et al. P75: transgenic expression of HIV-1 in Tg26 mice accelerates atherosclerosis; and implications for vascular dementia (abstr). J Neurovirol, 22(Suppl 1), 2016, s36.
117. Kim, W.K., Sun, Y., Do, H., et al. Monocyte heterogeneity underlying phenotypic changes in monocytes according to SIV disease stage. J Leukoc Biol 87 (2010), 557–567.
118. Pandrea, I., Xu, C., Stock, J.L., et al. Antibiotic antiinflammatory therapy transiently reduces inflammation and hypercoagulation in acutely SIV-infected pigtailed macaques. PLoS Pathog, 12, 2016, e1005384.
119. Yearley, J.H., Pearson, C., Shannon, R.P., Mansfield, K.G., Phenotypic variation in myocardial macrophage populations suggests a role for macrophage activation in SIV-associated cardiac disease. AIDS Res Hum Retroviruses 23 (2007), 515–524.
120. + macrophages in hearts of simian immunodeficiency virus-infected monkeys correlate with cardiac pathology and fibrosis. AIDS Res Hum Retroviruses 30 (2014), 685–694.
121. Panigrahi, S., Freeman, M.L., Funderburg, N.T., et al. SIV/SHIV infection triggers vascular inflammation, diminished expression of Krüppel-like factor 2 and endothelial dysfunction. J Infect Dis 213 (2016), 1419–1427.
122. Mansfield, K.G., Carville, A., Wachtman, L., et al. A diet high in saturated fat and cholesterol accelerates simian immunodeficiency virus disease progression. J Infect Dis 196 (2007), 1202–1210.
123. Banach, M., Dinca, M., Ursoniu, S., et al., for the Lipid Blood Pressure Meta-analysis Collaboration Group. A PRISMA-compliant systematic review and meta-analysis of randomized controlled trials investigating the effects of statin therapy on plasma lipid concentrations in HIV-infected patients. Pharmacol Res 111 (2016), 343–356.
124. Aberg, J.A., Sponseller, C.A., Ward, D.J., Kryzhanovski, V.A., Campbell, S.C., Thompson, M.A., Pitavastatin versus pravastatin in adults with HIV-1 infection and dyslipidemia (INTREPID): 12 week and 52 week results of a phase 4, multicentre, randomised, double-blind, superiority trial. Lancet HIV, 2017 Apr 12 [E-pub ahead of print].
125. Gilbert, J.M., Fitch, K.V., Grinspoon, S.K., HIV-related cardiovascular disease, statins, and the REPRIEVE Trial. Top Antivir Med 23 (2015), 146–149.
126. Hsue P, Deeks SG, Amorina E. IL-1β inhibition significantly reduces atherosclerotic inflammation in treated HIV. Paper presented at: Conference on Retroviruses and Opportunistic Infections (CROI); February 13–16, 2017; Seattle, WA.
127. Hileman, C.O., Turner, R., Funderburg, N.T., Semba, R.D., McComsey, G.A., Changes in oxidized lipids drive the improvement in monocyte activation and vascular disease after statin therapy in HIV. AIDS 30 (2016), 65–73.
128. Longenecker, C.T., Sattar, A., Gilkeson, R., McComsey, G.A., Rosuvastatin slows progression of subclinical atherosclerosis in patients with treated HIV infection. AIDS 30 (2016), 2195–2203.
129. Feng, D., Dai, S., Liu, F., et al. Cre-inducible human CD59 mediates rapid cell ablation after intermedilysin administration. J Clin Invest 126 (2016), 2321–2333.
130. Hu, W., Ferris, S.P., Tweten, R.K., et al. Rapid conditional targeted ablation of cells expressing human CD59 in transgenic mice by intermedilysin. Nat Med 14 (2008), 98–103.
131. de Arruda Falcão, C., Zirpoli, J.C., Albuquerque, V.M., et al. Association of biomarkers with atherosclerosis and risk for coronary artery disease in patients with HIV. Arq Bras Cardiol 99 (2012), 971–978.
132. Goulenok, T., Boyd, A., Larsen, M., et al., for the CHIC Study group. Increased carotid intima-media thickness is not associated with T-cell activation nor with cytomegalovirus in HIV-infected never-smoker patients. AIDS 29 (2015), 287–293.
133. Longenecker, C.T., Jiang, Y., Yun, C.H., et al. Perivascular fat, inflammation, and cardiovascular risk in HIV-infected patients on antiretroviral therapy. Int J Cardiol 168 (2013), 4039–4045.
134. + cells are not associated with carotid artery intima-media thickness progression in chronic HIV-positive subjects. Antiviral Ther 17 (2012), 557–563.
135. Rönsholt, F.F., Ostrowski, S.R., Katzenstein, T.L., Ullum, H., Gerstoft, J., T cell subsets in HIV infected patients after successful combination antiretroviral therapy: impact on survival after 12 years. PloS One, 7, 2012, e39356.