Background Mitochondria are the main source of reactive oxygen species (ROS). Human mitochondrial haplogroups are linked to differences in ROS production and oxidative-stress induced inflammation that may influence disease pathogenesis, including coronary artery disease (CAD). We previously showed that traffic-related air pollutants were associated with biomarkers of systemic inflammation in a cohort panel of subjects with CAD in the Los Angeles air basin. Objective We tested whether air pollutant exposure-associated inflammation was stronger in mitochondrial haplogroup H than U (high versus low ROS production) in this panel (38 subjects and 417 observations). Methods Inflammation biomarkers were measured weekly in each subject (≤12 weeks), including interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), C-reactive protein, interleukin-6 soluble receptor and tumor necrosis factor-soluble receptor II. We determined haplogroup by restriction fragment length polymorphism analysis. Air pollutants included nitrogen oxides (NOx), carbon monoxide (CO), organic carbon, elemental and black carbon (EC, BC); and particulate matter mass, three size fractions (<0.25 μm, 0.25–2.5 μm, and 2.5–10 μm in aerodynamic diameter). Particulate matter extracts were analyzed for organic compounds, including polycyclic aromatic hydrocarbons (PAH), and in vitro oxidative potential of aqueous extracts. Associations between exposures and biomarkers, stratified by haplogroup, were analyzed by mixed-effects models. Results IL-6 and TNF-α were associated with traffic-related air pollutants (BC, CO, NOx and PAH), and with mass and oxidative potential of quasi-ultrafine particles <0.25 μm. These associations were stronger for haplogroup H than haplogroup U. Conclusions Results suggest that mitochondrial haplogroup U is a novel protective factor for air pollution-related systemic inflammation in this small group of subjects.
References
[1]
Brook RD, Rajagopalan S, Pope CA 3rd, Brook JR, Bhatnagar A, et al. (2010) Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation 121: 2331–2378.
[2]
Pope CA 3rd, Muhlestein JB, May HT, Renlund DG, Anderson JL, et al. (2006) Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution. Circulation 114: 2443–2448.
[3]
Bhaskaran K, Hajat S, Haines A, Herrett E, Wilkinson P, et al. (2009) Effects of air pollution on the incidence of myocardial infarction. Heart 95: 1746–1759.
[4]
Peters A, von Klot S, Heier M, Trentinaglia I, Hormann A, et al. (2004) Exposure to traffic and the onset of myocardial infarction. N Engl J Med 351: 1721–1730.
[5]
Ayres JG, Borm P, Cassee FR, Castranova V, Donaldson K, et al. (2008) Evaluating the toxicity of airborne particulate matter and nanoparticles by measuring oxidative stress potential–a workshop report and consensus statement. Inhal Toxicol 20: 75–99.
[6]
Delfino RJ, Staimer N, Vaziri ND (2011) Air pollution and circulating biomarkers of oxidative stress. Air Quality, Atmosphere & Health 4: 37–52.
[7]
Delfino RJ, Staimer N, Tjoa T, Gillen DL, Polidori A, et al. (2009) Air pollution exposures and circulating biomarkers of effect in a susceptible population: clues to potential causal component mixtures and mechanisms. Environ Health Perspect 117: 1232–1238.
[8]
Delfino RJ, Staimer N, Tjoa T, Arhami M, Polidori A, et al. (2010) Associations of primary and secondary organic aerosols with airway and systemic inflammation in an elderly panel cohort. Epidemiology 21: 892–902.
[9]
Delfino RJ, Staimer N, Tjoa T, Arhami M, Polidori A, et al. (2010) Association of biomarkers of systemic inflammation with organic components and source tracers in quasi-ultrafine particles. Environ Health Perspect 118: 756–762.
[10]
Hou L, Zhu ZZ, Zhang X, Nordio F, Bonzini M, et al. (2010) Airborne particulate matter and mitochondrial damage: a cross-sectional study. Environ Health 9: 48.
[11]
Li N, Sioutas C, Cho A, Schmitz D, Misra C, et al. (2003) Ultrafine particulate pollutants induce oxidative stress and mitochondrial damage. Environ Health Perspect 111: 455–460.
[12]
Hiura TS, Li N, Kaplan R, Horwitz M, Seagrave JC, et al. (2000) The role of a mitochondrial pathway in the induction of apoptosis by chemicals extracted from diesel exhaust particles. J Immunol 165: 2703–2711.
[13]
Soberanes S, Urich D, Baker CM, Burgess Z, Chiarella SE, et al. (2009) Mitochondrial complex III-generated oxidants activate ASK1 and JNK to induce alveolar epithelial cell death following exposure to particulate matter air pollution. J Biol Chem 284: 2176–2186.
[14]
Nohl H (1994) Generation of superoxide radicals as byproduct of cellular respiration. Ann Biol Clin (Paris) 52: 199–204.
[15]
Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29: 222–230.
[16]
Madamanchi NR, Runge MS (2007) Mitochondrial dysfunction in atherosclerosis. Circ Res 100: 460–473.
[17]
Brand MD (2000) Uncoupling to survive? The role of mitochondrial inefficiency in ageing. Exp Gerontol 35: 811–820.
[18]
Ruiz-Pesini E, Mishmar D, Brandon M, Procaccio V, Wallace DC (2004) Effects of purifying and adaptive selection on regional variation in human mtDNA. Science 303: 223–226.
[19]
Khusnutdinova E, Gilyazova I, Ruiz-Pesini E, Derbeneva O, Khusainova R, et al. (2008) A mitochondrial etiology of neurodegenerative diseases: evidence from Parkinson's disease. Ann N Y Acad Sci 1147: 1–20.
[20]
van der Walt JM, Nicodemus KK, Martin ER, Scott WK, Nance MA, et al. (2003) Mitochondrial polymorphisms significantly reduce the risk of Parkinson disease. Am J Hum Genet 72: 804–811.
[21]
Delfino RJ, Tjoa T, Gillen DL, Staimer N, Polidori A, et al. (2010) Traffic-related air pollution and blood pressure in elderly subjects with coronary artery disease. Epidemiology 21: 396–404.
[22]
Sioutas C, Delfino RJ, Singh M (2005) Exposure assessment for atmospheric ultrafine particles (UFPs) and implications in epidemiologic research. Environ Health Perspect 113: 947–955.
[23]
Torroni A, Huoponen K, Francalacci P, Petrozzi M, Morelli L, et al. (1996) Classification of European mtDNAs from an analysis of three European populations. Genetics 144: 1835–1850.
[24]
Stone EA, Snyder DC, Sheesley RJ, Sullivan AP, Weber RJ, et al. (2008) Source apportionment of fine organic aerosol in Mexico City during the MILAGRO experiment 2006. Atmospheric Chemistry and Physics 8: 1249–1259.
[25]
Weber RJ, Sullivan AP, Peltier RE, Russell A, Yan B, et al. (2007) A study of secondary organic aerosol formation in the anthropogenic-influenced southeastern United States. J Geophys Res 112: D13302.
[26]
Docherty KS, Stone EA, Ulbrich IM, DeCarlo PF, Snyder DC, et al. (2008) Apportionment of Primary and Secondary Organic Aerosols in Southern California during the 2005 Study of Organic Aerosols in Riverside (SOAR-1). Environ Sci Technol 42: 7655–7662.
[27]
Sannigrahi P, Sullivan AP, Weber RJ, Ingall ED (2005) Characterization of Water-Soluble Organic Carbon in Urban Atmospheric Aerosols Using Solid-State 13C NMR Spectroscopy. Environ Sci Technol 40: 666–672.
[28]
Arhami M, Minguillon MC, Polidori A, Schauer JJ, Delfino RJ, et al. (2010) Organic compound characterization and source apportionment of indoor and outdoor quasi-ultrafine particulate matter in retirement homes of the Los Angeles Basin. Indoor Air 20: 17–30.
[29]
Landreman AP, Shafer MM, Hannigan MP, Schauer JJ (2008) A Macrophage-Based Method for the Assessment of the Reactive Oxygen Species (ROS) Activity of Atmospheric Particulate Matter (PM) and Application to Routine (Daily-24 h) Aerosol Monitoring Studies. Aerosol Science and Technology 42: 946–957.
[30]
Bender R, Lange S (2001) Adjusting for multiple testing–when and how? J Clin Epidemiol 54: 343–349.
[31]
Lee IT, Yang CM (2012) Role of NADPH oxidase/ROS in pro-inflammatory mediators-induced airway and pulmonary diseases. Biochem Pharmacol 84: 581–590.
[32]
Naik E, Dixit VM (2011) Mitochondrial reactive oxygen species drive proinflammatory cytokine production. J Exp Med 208: 417–420.
[33]
Li R, Ning Z, Cui J, Khalsa B, Ai L, et al. (2009) Ultrafine particles from diesel engines induce vascular oxidative stress via JNK activation. Free Radic Biol Med 46: 775–782.
[34]
Mo Y, Wan R, Feng L, Chien S, Tollerud DJ, et al. (2012) Combination effects of cigarette smoke extract and ambient ultrafine particles on endothelial cells. Toxicol In Vitro 26: 295–303.
[35]
Mutlu EA, Engen PA, Soberanes S, Urich D, Forsyth CB, et al. (2011) Particulate matter air pollution causes oxidant-mediated increase in gut permeability in mice. Part Fibre Toxicol 8: 19.
[36]
Bulua AC, Simon A, Maddipati R, Pelletier M, Park H, et al. (2011) Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS). J Exp Med 208: 519–533.
[37]
Singh T, Newman AB (2011) Inflammatory markers in population studies of aging. Ageing Res Rev 10: 319–329.
[38]
Pai JK, Pischon T, Ma J, Manson JE, Hankinson SE, et al. (2004) Inflammatory markers and the risk of coronary heart disease in men and women. N Engl J Med 351: 2599–2610.
[39]
Raman K, Chong M, Akhtar-Danesh GG, D'Mello M, Hasso R, et al. (2013) Genetic markers of inflammation and their role in cardiovascular disease. Can J Cardiol 29: 67–74.
[40]
Fisman EZ, Benderly M, Esper RJ, Behar S, Boyko V, et al. (2006) Interleukin-6 and the risk of future cardiovascular events in patients with angina pectoris and/or healed myocardial infarction. Am J Cardiol 98: 14–18.
[41]
Morita M, Yano S, Yamaguchi T, Yamauchi M, Sugimoto T (2011) Phenylacetic acid stimulates reactive oxygen species generation and tumor necrosis factor-alpha secretion in vascular endothelial cells. Ther Apher Dial 15: 147–150.
[42]
Morita M, Yano S, Yamaguchi T, Sugimoto T (2012) Advanced glycation end products-induced reactive oxygen species generation is partly through NF-kappa B activation in human aortic endothelial cells. J Diabetes Complications
[43]
Alonso JR, Cardellach F, Lopez S, Casademont J, Miro O (2003) Carbon monoxide specifically inhibits cytochrome c oxidase of human mitochondrial respiratory chain. Pharmacol Toxicol 93: 142–146.
[44]
Woods JA, Vieira VJ, Keylock KT (2009) Exercise, inflammation, and innate immunity. Immunol Allergy Clin North Am 29: 381–393.
[45]
Canter JA, Robbins GK, Selph D, Clifford DB, Kallianpur AR, et al. (2010) African mitochondrial DNA subhaplogroups and peripheral neuropathy during antiretroviral therapy. J Infect Dis 201: 1703–1707.
[46]
De Luca A, Nasi M, Di Giambenedetto S, Cozzi-Lepri A, Pinti M, et al. (2012) Mitochondrial DNA haplogroups and incidence of lipodystrophy in HIV-infected patients on long-term antiretroviral therapy. J Acquir Immune Defic Syndr 59: 113–120.
[47]
Di Lorenzo C, Pierelli F, Coppola G, Grieco GS, Rengo C, et al. (2009) Mitochondrial DNA haplogroups influence the therapeutic response to riboflavin in migraineurs. Neurology 72: 1588–1594.
[48]
Gomez-Duran A, Pacheu-Grau D, Lopez-Gallardo E, Diez-Sanchez C, Montoya J, et al. (2010) Unmasking the causes of multifactorial disorders: OXPHOS differences between mitochondrial haplogroups. Hum Mol Genet 19: 3343–3353.
