{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T19:51:21Z","timestamp":1791402681847,"version":"4.3.3"},"reference-count":73,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2019,9,23]],"date-time":"2019-09-23T00:00:00Z","timestamp":1569196800000},"content-version":"vor","delay-in-days":2,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/100012429","name":"LSU School of Veterinary Medicine","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100012429","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2019,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Combination antiretroviral therapy (cART) has improved the life expectancy of HIV patients, thus increasing the number of people living with HIV (PLWH). However, cardiovascular diseases (CVD) are now one of the most prevalent causes of death among PLWH. Nucleoside reverse transcriptase inhibitors (NRTIs) are the backbone of cART, and the emtricitabine (FTC) and tenofovir disoproxil fumarate (TDF) coformulation is commonly used. In prior studies, acute NRTI treatment-induced endothelial dysfunction, increased reactive oxygen species production, and mitophagic activity, suggesting that mitochondrial dysfunction may be critical to NRTI-induced endothelial dysfunction. Mitochondrial dysfunction plays a causal role in endothelial senescence, whereas premature endothelial senescence can promote the development of CVD. We hypothesize that for chronic NRTI treatment, a disruption in mitochondrial homeostasis leads to premature endothelial senescence and predisposes PLWH to CVD. We used human aortic endothelial cells (HAEC) and HIV-1 transgenic (Tg26) mice to test the interrelationship between mitochondrial and vascular dysfunction after chronic NRTI treatment in vitro and in vivo. Mitochondrial DNA copy number was decreased in late-passage HAEC treated with NRTIs, and senescence-associated \u03b2-galactosidase accumulation was elevated. In late-passage HAEC, NRTIs decreased the activity of Parkin-mediated mitophagy. In Tg26 mice treated with FTC, plasma nitrite levels were decreased. Endothelium-dependent vasodilation in NRTI-treated Tg26 mice was also reduced. Our work suggests that long-term use of NRTI may disrupt mitochondrial homeostasis, induce premature endothelial senescence, and impair vascular function.<\/jats:p>","DOI":"10.1093\/toxsci\/kfz203","type":"journal-article","created":{"date-parts":[[2019,9,18]],"date-time":"2019-09-18T11:37:19Z","timestamp":1568806639000},"page":"445-456","source":"Crossref","is-referenced-by-count":19,"title":["Chronic Nucleoside Reverse Transcriptase Inhibitors Disrupt Mitochondrial Homeostasis and Promote Premature Endothelial Senescence"],"prefix":"10.1093","volume":"172","author":[{"given":"Yi-Fan","family":"Chen","sequence":"first","affiliation":[{"name":"Comparative Biomedical Sciences, LSU School of Veterinary Medicine, Baton Rouge, Louisiana 70808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James E","family":"Stampley","sequence":"additional","affiliation":[{"name":"College of Human Sciences and Education, LSU School of Kinesiology, Baton Rouge, Louisiana 70803"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian A","family":"Irving","sequence":"additional","affiliation":[{"name":"College of Human Sciences and Education, LSU School of Kinesiology, Baton Rouge, Louisiana 70803"},{"name":"Pennington Biomedical Research Center, Baton Rouge, Louisiana, 70808"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tammy R","family":"Dugas","sequence":"additional","affiliation":[{"name":"Comparative Biomedical Sciences, LSU School of Veterinary Medicine, Baton Rouge, Louisiana 70808"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2019,9,21]]},"reference":[{"key":"2019112509003747500_kfz203-B1","author":"AIDSinfo","year":"2019"},{"key":"2019112509003747500_kfz203-B2","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1080\/15548627.2018.1532259","article-title":"PRKN-regulated mitophagy and cellular senescence during COPD pathogenesis","volume":"15","author":"Araya","year":"2019","journal-title":"Autophagy"},{"key":"2019112509003747500_kfz203-B3","doi-asserted-by":"crossref","first-page":"960","DOI":"10.1161\/01.RES.86.9.960","article-title":"Hydrogen peroxide- and peroxynitrite-induced mitochondrial DNA damage and dysfunction in vascular endothelial and smooth muscle cells","volume":"86","author":"Ballinger","year":"2000","journal-title":"Circ Res"},{"key":"2019112509003747500_kfz203-B4","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1016\/j.biocel.2004.10.013","article-title":"The signals and pathways activating cellular senescence","volume":"37","author":"Ben-Porath","year":"2005","journal-title":"Int. J. Biochem. Cell Biol"},{"key":"2019112509003747500_kfz203-B5","doi-asserted-by":"crossref","first-page":"1025","DOI":"10.1038\/ijo.2011.201","article-title":"Mitochondrial lipid oxidation is impaired in cultured myotubes from obese humans","volume":"36","author":"Boyle","year":"2012","journal-title":"Int. J. Obes"},{"key":"2019112509003747500_kfz203-B6","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1016\/j.freeradbiomed.2004.05.034","article-title":"Mitochondrial superoxide: Production, biological effects, and activation of uncoupling proteins","volume":"37","author":"Brand","year":"2004","journal-title":"Free Radic. Biol. Med"},{"key":"2019112509003747500_kfz203-B7","doi-asserted-by":"crossref","first-page":"940","DOI":"10.1006\/viro.1994.1416","article-title":"Patterns of HIV-1 mRNA expression in transgenic mice are tissue-dependent","volume":"202","author":"Bruggeman","year":"1994","journal-title":"Virology"},{"key":"2019112509003747500_kfz203-B8","doi-asserted-by":"crossref","first-page":"C1675","DOI":"10.1152\/ajpcell.00092.2002","article-title":"Endothelial cells maintain a reduced redox environment even as mitochondrial function declines","volume":"283","author":"Carlisle","year":"2002","journal-title":"Am. J. Physiol. Cell Physiol"},{"key":"2019112509003747500_kfz203-B9","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1177\/135965350801300103","article-title":"Contribution of mitochondrial dysfunction and oxidative stress to cellular premature senescence induced by antiretroviral thymidine analogues","volume":"13","author":"Caron","year":"2008","journal-title":"Antivir. Ther"},{"key":"2019112509003747500_kfz203-B10","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1128\/AAC.50.4.1304-1310.2006","article-title":"Pharmacokinetics of tenofovir disoproxil fumarate and ritonavir-boosted saquinavir mesylate administered alone or in combination at steady state","volume":"50","author":"Chittick","year":"2006","journal-title":"Antimicrob. Agents Chemother"},{"key":"2019112509003747500_kfz203-B11","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.mad.2018.07.008","article-title":"HIV antiretroviral therapy drugs induce premature senescence and altered physiology in HUVECs","volume":"175","author":"Cohen","year":"2018","journal-title":"Mech. Ageing Dev"},{"key":"2019112509003747500_kfz203-B12","doi-asserted-by":"crossref","first-page":"281.","DOI":"10.3389\/fnagi.2017.00281","article-title":"Astrocyte senescence and metabolic changes in response to HIV antiretroviral therapy drugs","volume":"9","author":"Cohen","year":"2017","journal-title":"Front. Aging Neurosci"},{"key":"2019112509003747500_kfz203-B13","doi-asserted-by":"crossref","first-page":"913","DOI":"10.18632\/aging.100622","article-title":"Age-associated stresses induce an anti-inflammatory senescent phenotype in endothelial cells","volume":"5","author":"Coleman","year":"2013","journal-title":"Aging"},{"key":"2019112509003747500_kfz203-B14","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1016\/j.cell.2013.06.037","article-title":"Role of pfkfb3-driven glycolysis in vessel sprouting","volume":"154","author":"De Bock","year":"2013","journal-title":"Cell"},{"key":"2019112509003747500_kfz203-B15","doi-asserted-by":"crossref","first-page":"4905","DOI":"10.1128\/AAC.00120-11","article-title":"Concentrations of tenofovir and emtricitabine in saliva: Implications for preexposure prophylaxis of oral HIV acquisition","volume":"55","author":"de Lastours","year":"2011","journal-title":"Antimicrob. Agents Chemother"},{"key":"2019112509003747500_kfz203-B16","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/0042-6822(91)90759-5","article-title":"HIV-associated nephropathy in transgenic mice expressing HIV-1 genes","volume":"185","author":"Dickie","year":"1991","journal-title":"Virology"},{"key":"2019112509003747500_kfz203-B17","doi-asserted-by":"crossref","first-page":"9363","DOI":"10.1073\/pnas.92.20.9363","article-title":"A biomarker that identifies senescent human cells in culture and in aging skin in vivo","volume":"92","author":"Dimri","year":"1995","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"2019112509003747500_kfz203-B18","doi-asserted-by":"crossref","first-page":"e12773.","DOI":"10.1111\/acel.12773","article-title":"Restoring mitochondrial DNA copy number preserves mitochondrial function and delays vascular aging in mice","volume":"17","author":"Foote","year":"2018","journal-title":"Aging Cell"},{"key":"2019112509003747500_kfz203-B19","doi-asserted-by":"crossref","first-page":"2297","DOI":"10.1016\/j.bbamcr.2012.08.007","article-title":"Mitophagy is triggered by mild oxidative stress in a mitochondrial fission dependent manner","volume":"1823","author":"Frank","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"2019112509003747500_kfz203-B20","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1177\/2047487315579291","article-title":"An updated prediction model of the global risk of cardiovascular disease in HIV-positive persons: The data-collection on adverse effects of anti-HIV drugs (d:A:D) study","volume":"23","author":"Friis-Moller","year":"2016","journal-title":"Eur. J. Prev. Cardiol"},{"key":"2019112509003747500_kfz203-B21","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1097\/00002030-200305230-00010","article-title":"Cardiovascular disease risk factors in HIV patients-association with antiretroviral therapy. Results from the dad study","volume":"17","author":"Friis-Moller","year":"2003","journal-title":"Aids"},{"key":"2019112509003747500_kfz203-B22","first-page":"1525","article-title":"Comorbidities among us patients with prevalent HIV infection-a trend analysis","volume":"216","author":"Gallant","year":"2017","journal-title":"J. Infect. Dis"},{"key":"2019112509003747500_kfz203-B23","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.antiviral.2014.09.010","article-title":"Overexpression of mitochondrial antioxidant manganese superoxide dismutase (MnSOD) provides protection against azt- or 3tc-induced endothelial dysfunction","volume":"111","author":"Glover","year":"2014","journal-title":"Antiviral Res"},{"key":"2019112509003747500_kfz203-B24","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.1016\/S0140-6736(08)60423-7","article-title":"Use of nucleoside reverse transcriptase inhibitors and risk of myocardial infarction in HIV-infected patients enrolled in the d:A:D study: A multi-cohort collaboration","volume":"371","author":"Group","year":"2008","journal-title":"Lancet"},{"key":"2019112509003747500_kfz203-B25","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/320454a0","article-title":"Superoxide anion is involved in the breakdown of endothelium-derived vascular relaxing factor","volume":"320","author":"Gryglewski","year":"1986","journal-title":"Nature"},{"key":"2019112509003747500_kfz203-B26","doi-asserted-by":"crossref","first-page":"e93357.","DOI":"10.1371\/journal.pone.0093357","article-title":"Endothelial dysfunction and brachial intima-media thickness: Long term cardiovascular risk with claudication related to peripheral arterial disease: A prospective analysis","volume":"9","author":"Hafner","year":"2014","journal-title":"PLoS One"},{"key":"2019112509003747500_kfz203-B27","doi-asserted-by":"crossref","first-page":"1067","DOI":"10.1128\/AAC.46.4.1067-1072.2002","article-title":"Phenotypic susceptibilities to tenofovir in a large panel of clinically derived human immunodeficiency virus type 1 isolates","volume":"46","author":"Harrigan","year":"2002","journal-title":"Antimicrob. Agents Chemother"},{"key":"2019112509003747500_kfz203-B28","doi-asserted-by":"crossref","first-page":"e13647.","DOI":"10.14814\/phy2.13647","article-title":"Effects of HIV-1 gp120 and tat on endothelial cell sensescence and senescence-associated microRNAs","volume":"6","author":"Hijmans","year":"2018","journal-title":"Physiol. Rep"},{"key":"2019112509003747500_kfz203-B29","doi-asserted-by":"crossref","first-page":"749","DOI":"10.1093\/nar\/gkn993","article-title":"Reactive oxygen species regulate DNA copy number in isolated yeast mitochondria by triggering recombination-mediated replication","volume":"37","author":"Hori","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2019112509003747500_kfz203-B30","doi-asserted-by":"crossref","first-page":"2308.","DOI":"10.1038\/ncomms3308","article-title":"Cytosolic p53 inhibits Parkin-mediated mitophagy and promotes mitochondrial dysfunction in the mouse heart","volume":"4","author":"Hoshino","year":"2013","journal-title":"Nat. Commun"},{"key":"2019112509003747500_kfz203-B31","doi-asserted-by":"crossref","first-page":"919","DOI":"10.1042\/bj20040095","article-title":"Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts","volume":"380","author":"Hutter","year":"2004","journal-title":"Biochem. J"},{"key":"2019112509003747500_kfz203-B32","doi-asserted-by":"crossref","first-page":"22019","DOI":"10.1074\/jbc.M113.467530","article-title":"Parkin-catalyzed ubiquitin-ester transfer is triggered by pink1-dependent phosphorylation","volume":"288","author":"Iguchi","year":"2013","journal-title":"J. Biol. Chem"},{"key":"2019112509003747500_kfz203-B33","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1080\/15548627.2015.1017190","article-title":"Park2-mediated mitophagy is involved in regulation of HBEC senescence in COPD pathogenesis","volume":"11","author":"Ito","year":"2015","journal-title":"Autophagy"},{"key":"2019112509003747500_kfz203-B34","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1016\/j.taap.2007.06.010","article-title":"HIV antiretroviral drug combination induces endothelial mitochondrial dysfunction and reactive oxygen species production, but not apoptosis","volume":"224","author":"Jiang","year":"2007","journal-title":"Toxicol. Appl. Pharmacol"},{"key":"2019112509003747500_kfz203-B35","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1097\/01.qai.0000228790.40235.0c","article-title":"Antiretrovirals induce direct endothelial dysfunction in vivo","volume":"42","author":"Jiang","year":"2006","journal-title":"J. Acquir. Immune Defic. Syndr"},{"key":"2019112509003747500_kfz203-B36","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1093\/toxsci\/kfq213","article-title":"Antiretrovirals induce endothelial dysfunction via an oxidant-dependent pathway and promote neointimal hyperplasia","volume":"117","author":"Jiang","year":"2010","journal-title":"Toxicol. Sci"},{"key":"2019112509003747500_kfz203-B37","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1093\/cvr\/cvq013","article-title":"HIV gp120 induces endothelial dysfunction in tumour necrosis factor-alpha-activated porcine and human endothelial cells","volume":"87","author":"Jiang","year":"2010","journal-title":"Cardiovasc. Res"},{"key":"2019112509003747500_kfz203-B38","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1083\/jcb.201008084","article-title":"Mitochondrial membrane potential regulates pink1 import and proteolytic destabilization by parl","volume":"191","author":"Jin","year":"2010","journal-title":"J. Cell Biol"},{"key":"2019112509003747500_kfz203-B39","doi-asserted-by":"crossref","first-page":"3565","DOI":"10.1016\/j.celrep.2018.05.054","article-title":"Redox regulation of mitochondrial fission protein drp1 by protein disulfide isomerase limits endothelial senescence","volume":"23","author":"Kim","year":"2018","journal-title":"Cell Rep"},{"key":"2019112509003747500_kfz203-B40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12012-008-9029-8","article-title":"Long-term exposure to azt, but not d4t, increases endothelial cell oxidative stress and mitochondrial dysfunction","volume":"9","author":"Kline","year":"2009","journal-title":"Cardiovasc. Toxicol"},{"key":"2019112509003747500_kfz203-B41","doi-asserted-by":"crossref","first-page":"44373.","DOI":"10.1038\/srep44373","article-title":"Nix restores mitophagy and mitochondrial function to protect against pink1\/Parkin-related Parkinson's disease","volume":"7","author":"Koentjoro","year":"2017","journal-title":"Sci. Rep"},{"key":"2019112509003747500_kfz203-B42","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1002\/em.20223","article-title":"A brief overview of mechanisms of mitochondrial toxicity from NRTIs","volume":"48","author":"Kohler","year":"2007","journal-title":"Environ. Mol. Mutagen"},{"key":"2019112509003747500_kfz203-B43","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1158\/0008-5472.177.65.1","article-title":"Glycolytic enzymes can modulate cellular life span","volume":"65","author":"Kondoh","year":"2005","journal-title":"Cancer Res"},{"key":"2019112509003747500_kfz203-B44","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1242\/jcs.01097","article-title":"Chronic oxidative stress compromises telomere integrity and accelerates the onset of senescence in human endothelial cells","volume":"117","author":"Kurz","year":"2004","journal-title":"J. Cell Sci"},{"key":"2019112509003747500_kfz203-B45","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.arr.2014.07.001","article-title":"The mitochondrial genome in aging and senescence","volume":"18","author":"Lauri","year":"2014","journal-title":"Ageing Res. Rev"},{"key":"2019112509003747500_kfz203-B46","doi-asserted-by":"crossref","first-page":"296","DOI":"10.1016\/j.atherosclerosis.2012.04.010","article-title":"Notch activation induces endothelial cell senescence and pro-inflammatory response: Implication of notch signaling in atherosclerosis","volume":"225","author":"Liu","year":"2012","journal-title":"Atherosclerosis"},{"key":"2019112509003747500_kfz203-B47","doi-asserted-by":"crossref","first-page":"1194","DOI":"10.1016\/j.cell.2013.05.039","article-title":"The hallmarks of aging","volume":"153","author":"Lopez-Otin","year":"2013","journal-title":"Cell"},{"key":"2019112509003747500_kfz203-B48","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1097\/01.mnh.0000222688.69217.8e","article-title":"Animal models of HIV-associated nephropathy","volume":"15","author":"Lu","year":"2006","journal-title":"Curr. Opin. Nephrol. Hypertens"},{"key":"2019112509003747500_kfz203-B49","doi-asserted-by":"crossref","first-page":"4087","DOI":"10.1128\/AAC.00816-06","article-title":"In vitro human immunodeficiency virus type 1 resistance selections with combinations of tenofovir and emtricitabine or abacavir and lamivudine","volume":"50","author":"Margot","year":"2006","journal-title":"Antimicrob. Agents Chemother"},{"key":"2019112509003747500_kfz203-B50","first-page":"1097","article-title":"Review of tenofovir-emtricitabine","volume":"3","author":"Masho","year":"2007","journal-title":"Ther. Clin. Risk Manag"},{"key":"2019112509003747500_kfz203-B51","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.abb.2018.12.002","article-title":"Proton leak regulates mitochondrial reactive oxygen species generation in endothelial cell activation and inflammation\u2014A novel concept","volume":"662","author":"Nanayakkara","year":"2019","journal-title":"Arch. Biochem. Biophys"},{"key":"2019112509003747500_kfz203-B52","doi-asserted-by":"crossref","first-page":"795","DOI":"10.1083\/jcb.200809125","article-title":"Parkin is recruited selectively to impaired mitochondria and promotes their autophagy","volume":"183","author":"Narendra","year":"2008","journal-title":"J. Cell Biol"},{"key":"2019112509003747500_kfz203-B53","doi-asserted-by":"crossref","first-page":"e1000298.","DOI":"10.1371\/journal.pbio.1000298","article-title":"Pink1 is selectively stabilized on impaired mitochondria to activate Parkin","volume":"8","author":"Narendra","year":"2010","journal-title":"PLoS Biol"},{"key":"2019112509003747500_kfz203-B54","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1038\/embor.2009.256","article-title":"Nix is a selective autophagy receptor for mitochondrial clearance","volume":"11","author":"Novak","year":"2010","journal-title":"EMBO Rep"},{"key":"2019112509003747500_kfz203-B55","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1016\/S0741-5214(03)00770-5","article-title":"HIV tat protein causes endothelial dysfunction in porcine coronary arteries","volume":"38","author":"Paladugu","year":"2003","journal-title":"J. Vasc. Surg"},{"key":"2019112509003747500_kfz203-B56","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.exger.2014.01.021","article-title":"Mitochondrial homeostasis: The interplay between mitophagy and mitochondrial biogenesis","volume":"56","author":"Palikaras","year":"2014","journal-title":"Exp. Gerontol"},{"key":"2019112509003747500_kfz203-B57","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/j.thromres.2011.03.025","article-title":"The nuclear factor-kappa b pathway in atherosclerosis: A potential therapeutic target for atherothrombotic vascular disease","volume":"128","author":"Pamukcu","year":"2011","journal-title":"Thromb. Res"},{"key":"2019112509003747500_kfz203-B58","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1097\/01.qai.0000245886.51262.67","article-title":"Tenofovir disoproxil fumarate, emtricitabine, and efavirenz versus fixed-dose zidovudine\/lamivudine and efavirenz in antiretroviral-naive patients: Virologic, immunologic, and morphologic changes\u2014A 96-week analysis","volume":"43","author":"Pozniak","year":"2006","journal-title":"J. Acquir. Immune Defic. Syndr"},{"key":"2019112509003747500_kfz203-B59","doi-asserted-by":"crossref","first-page":"2627","DOI":"10.1158\/0008-5472.CAN-03-0846","article-title":"The tumor suppressor p53 down-regulates glucose transporters glut1 and glut4 gene expression","volume":"64","author":"Schwartzenberg-Bar-Yoseph","year":"2004","journal-title":"Cancer Res"},{"key":"2019112509003747500_kfz203-B60","doi-asserted-by":"crossref","first-page":"19500","DOI":"10.1073\/pnas.0708818104","article-title":"Nix is required for programmed mitochondrial clearance during reticulocyte maturation","volume":"104","author":"Schweers","year":"2007","journal-title":"Proc. Natl. Acad. Sci. U.S.A"},{"key":"2019112509003747500_kfz203-B61","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1159\/000134943","article-title":"Mechanisms of zidovudine-induced mitochondrial toxicity and myopathy","volume":"82","author":"Scruggs","year":"2008","journal-title":"Pharmacology"},{"key":"2019112509003747500_kfz203-B62","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1097\/00002030-200109280-00009","article-title":"Mitochondrial DNA decrease in subcutaneous adipose tissue of HIV-infected individuals with peripheral lipoatrophy","volume":"15","author":"Shikuma","year":"2001","journal-title":"Aids"},{"key":"2019112509003747500_kfz203-B63","doi-asserted-by":"crossref","first-page":"2539","DOI":"10.1093\/nar\/gkp100","article-title":"Oxidative stress induces degradation of mitochondrial DNA","volume":"37","author":"Shokolenko","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"2019112509003747500_kfz203-B64","first-page":"153","article-title":"Nucleoside analogue-associated peripheral neuropathy in human immunodeficiency virus infection","volume":"9","author":"Simpson","year":"1995","journal-title":"J. Acquir. Immune Defic. Syndr. Hum. Retrovirol"},{"key":"2019112509003747500_kfz203-B65","doi-asserted-by":"crossref","first-page":"175.","DOI":"10.3389\/fphys.2014.00175","article-title":"Mitochondria, endothelial cell function, and vascular diseases","volume":"5","author":"Tang","year":"2014","journal-title":"Front. Physiol"},{"key":"2019112509003747500_kfz203-B66","doi-asserted-by":"crossref","first-page":"247","DOI":"10.1007\/s10522-008-9134-x","article-title":"Premature senescence of human endothelial cells induced by inhibition of glutaminase","volume":"9","author":"Unterluggauer","year":"2008","journal-title":"Biogerontology"},{"key":"2019112509003747500_kfz203-B67","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/cvr\/cvq002","article-title":"Dipyridamole enhances ischaemia-induced arteriogenesis through an endocrine nitrite\/nitric oxide-dependent pathway","volume":"85","author":"Venkatesh","year":"2010","journal-title":"Cardiovasc. Res"},{"key":"2019112509003747500_kfz203-B68","doi-asserted-by":"crossref","first-page":"e91063.","DOI":"10.1371\/journal.pone.0091063","article-title":"Transfer of intracellular HIV nef to endothelium causes endothelial dysfunction","volume":"9","author":"Wang","year":"2014","journal-title":"PLoS One"},{"key":"2019112509003747500_kfz203-B69","doi-asserted-by":"crossref","first-page":"e0132499.","DOI":"10.1371\/journal.pone.0132499","article-title":"Pink1-Parkin-mediated mitophagy protects mitochondrial integrity and prevents metabolic stress-induced endothelial injury","volume":"10","author":"Wu","year":"2015","journal-title":"PLoS One"},{"key":"2019112509003747500_kfz203-B70","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1093\/toxsci\/kft105","article-title":"Nucleoside reverse transcriptase inhibitors induce a mitophagy-associated endothelial cytotoxicity that is reversed by coenzyme q10 cotreatment","volume":"134","author":"Xue","year":"2013","journal-title":"Toxicol. Sci"},{"key":"2019112509003747500_kfz203-B71","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1161\/01.RES.73.1.205","article-title":"Tumor necrosis factor downregulates an endothelial nitric oxide synthase mrna by shortening its half-life","volume":"73","author":"Yoshizumi","year":"1993","journal-title":"Circ. Res"},{"key":"2019112509003747500_kfz203-B72","doi-asserted-by":"crossref","first-page":"856","DOI":"10.1177\/0192623310378866","article-title":"Biomarkers of endothelial cell activation serve as potential surrogate markers for drug-induced vascular injury","volume":"38","author":"Zhang","year":"2010","journal-title":"Toxicol. Pathol"},{"key":"2019112509003747500_kfz203-B73","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/acel.12287","article-title":"Mitochondrial effectors of cellular senescence: Beyond the free radical theory of aging","volume":"14","author":"Ziegler","year":"2015","journal-title":"Aging Cell"}],"container-title":["Toxicological Sciences"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/academic.oup.com\/toxsci\/advance-article-pdf\/doi\/10.1093\/toxsci\/kfz203\/30112066\/kfz203.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/172\/2\/445\/31084136\/kfz203.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/academic.oup.com\/toxsci\/article-pdf\/172\/2\/445\/31084136\/kfz203.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,9,28]],"date-time":"2022-09-28T23:47:21Z","timestamp":1664408841000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/toxsci\/article\/172\/2\/445\/5572673"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,9,21]]},"references-count":73,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2019,9,21]]},"published-print":{"date-parts":[[2019,12,1]]}},"URL":"https:\/\/doi.org\/10.1093\/toxsci\/kfz203","relation":{},"ISSN":["1096-6080","1096-0929"],"issn-type":[{"value":"1096-6080","type":"print"},{"value":"1096-0929","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2019,12]]},"published":{"date-parts":[[2019,9,21]]}}}