Abstract
Fine particulate matter (PM2.5) has been considered a risk factor for cardiovascular diseases by inducing an oxidative and inflammatory phenotype. Besides, the reduction of 17β-estradiol (E2) levels during menopause is a natural risk for cardiovascular outcomes. During the E2 downfall, there is a high requirement of the 70-kDa heat shock proteins (HSP70), which present essential antioxidant, anti-inflammatory, and anti-senescence roles. We investigated if the ovariectomy, an animal model for menopause, could induce additional effects in cardiac health by impairing oxidative and heat shock response parameters of female rats chronically exposed to residual oil fly ash (ROFA; an inorganic fraction of PM2.5). Thus, ROFA was obtained from São Paulo (Brazil) and solubilized it in saline. Further, female Wistar rats were exposed to 50 μL of saline (control group) or ROFA solution (250 μg) (polluted) by intranasal instillation, 5 days/week, 12 weeks. At the 12th week, animals were subdivided into four groups (n = 6 p/group): control, OVX, polluted, and polluted + OVX. Control and polluted were submitted to false surgery, while OVX and polluted + OVX were ovariectomized. ROFA or saline exposure continued for 12 weeks. Ovariectomy reduced the cardiac catalase activity and iHSP70 expression in female rats exposed to ROFA. Neither plasma eHSP72 levels nor H-index (eHSP72 to cardiac iHSP70 ratio) was affected. In conclusion, ovariectomy reduces the cardiac cytoprotection and antioxidant defense, and enhances the susceptibility to premature cellular senescence in rats exposed to ROFA.
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The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
References
Aebi H (1984) Catalase in vitro Methods. Enzymol 105:121–126
Baldissera FG et al (2018) Subacute exposure to residual oil fly ash (ROFA) increases eHSP70 content and extracellular-to-intracellular HSP70 ratio: a relation with oxidative stress markers. Cell Stress Chaperones 23:1185–1192. https://doi.org/10.1007/s12192-018-0924-z
Bansal S, Chopra K (2014) Distinct role of estrogen receptor-alpha and beta on postmenopausal diabetes-induced vascular dysfunction. Gen Comp Endocrinol 206:51–59. https://doi.org/10.1016/j.ygcen.2014.06.013
Bendale DS, Karpe PA, Chhabra R, Shete SP, Shah H, Tikoo K (2013) 17-beta Oestradiol prevents cardiovascular dysfunction in post-menopausal metabolic syndrome by affecting SIRT1/AMPK/H3 acetylation. Br J Pharmacol 170:779–795. https://doi.org/10.1111/bph.12290
Braidy N, Guillemin GJ, Mansour H, Chan-Ling T, Poljak A, Grant R (2011) Age related changes in NAD+ metabolism oxidative stress and Sirt1 activity in wistar rats. PLoS One 6:e19194. https://doi.org/10.1371/journal.pone.0019194
Bruxel MA et al (2019) Chronic whole-body heat treatment relieves atherosclerotic lesions, cardiovascular and metabolic abnormalities, and enhances survival time restoring the anti-inflammatory and anti-senescent heat shock response in mice. Biochimie 156:33–46. https://doi.org/10.1016/j.biochi.2018.09.011
Buege JA, Aust SD (1978) Microsomal lipid peroxidation Methods. Enzymol 52:302–310
Chae SY, Lee M, Kim SW, Bae YH (2004) Protection of insulin secreting cells from nitric oxide induced cellular damage by crosslinked hemoglobin. Biomaterials 25:843–850
Chang Y, Chen TL, Sheu JR, Chen RM (2005) Suppressive effects of ketamine on macrophage functions. Toxicol Appl Pharmacol 204:27–35. https://doi.org/10.1016/j.taap.2004.08.011
Costa Beber LC et al (2020) The association of subchronic exposure to low concentration of PM2.5 and high-fat diet potentiates glucose intolerance development, by impairing adipose tissue antioxidant defense and eHSP72 levels. Environ Sci Pollut Res Int 27:32006–32016. https://doi.org/10.1007/s11356-020-09581-8
Costa-Beber LC, Hirsch GE, Heck TG, Ludwig MS (2020) Chaperone duality: the role of extracellular and intracellular HSP70 as a biomarker of endothelial dysfunction in the development of atherosclerosis. Arch Physiol Biochem:1–8. https://doi.org/10.1080/13813455.2020.1745850
Cui A et al (2019) VCAM-1-mediated neutrophil infiltration exacerbates ambient fine particle-induced lung injury. Toxicol Lett 302:60–74. https://doi.org/10.1016/j.toxlet.2018.11.002
Dai J, Sun C, Yao Z, Chen W, Yu L, Long M (2016) Exposure to concentrated ambient fine particulate matter disrupts vascular endothelial cell barrier function via the IL-6/HIF-1alpha signaling pathway. FEBS Open Bio 6:720–728. https://doi.org/10.1002/2211-5463.12077
Damiani RM, Piva MO, Petry MR, Saldiva PH, Tavares Duarte de Oliveira A, Rhoden CR (2012) Is cardiac tissue more susceptible than lung to oxidative effects induced by chronic nasotropic instillation of residual oil fly ash (ROFA)? Toxicol Mech Methods 22:533–539. https://doi.org/10.3109/15376516.2012.692109
Davel AP et al (2012) Endothelial dysfunction in the pulmonary artery induced by concentrated fine particulate matter exposure is associated with local but not systemic inflammation. Toxicology 295:39–46. https://doi.org/10.1016/j.tox.2012.02.004
De Maio A, Vazquez D (2013) Extracellular heat shock proteins: a new location, a new function. Shock 40:239–246. https://doi.org/10.1097/SHK.0b013e3182a185ab
de Oliveira-Fonoff AM et al (2017) The role of air pollution in myocardial remodeling. PLoS One 12:e0176084. https://doi.org/10.1371/journal.pone.0176084
EPA (2010) https://ofmpub.epa.gov/sor_internet/registry/termreg/searchandretrieve/termsandacronyms/search.do?search=&term=chronic&matchCriteria=Contains&checkedAcronym=true&checkedTerm=true&hasDefinitions=false%23formTop. Accessed Jan 2021
Furuyama A, Kanno S, Kobayashi T, Hirano S (2009) Extrapulmonary translocation of intratracheally instilled fine and ultrafine particles via direct and alveolar macrophage-associated routes. Arch Toxicol 83:429–437. https://doi.org/10.1007/s00204-008-0371-1
Galovic R, Flegar-Mestric Z, Vidjak V, Matokanovic M, Barisic K (2016) Heat shock protein 70 and antibodies to heat shock protein 60 are associated with cerebrovascular atherosclerosis. Clin Biochem 49:66–69. https://doi.org/10.1016/j.clinbiochem.2015.10.006
Ghio AJ, Silbajoris R, Carson JL, Samet JM (2002a) Biologic effects of oil fly ash. Environ Health Perspect 110(Suppl 1):89–94
Ghio AJ, Suliman HB, Carter JD, Abushamaa AM, Folz RJ (2002b) Overexpression of extracellular superoxide dismutase decreases lung injury after exposure to oil fly ash. Am J Physiol Lung Cell Mol Physiol 283:L211–L218. https://doi.org/10.1152/ajplung.00409.2001
Gil Lorenzo AF, Bocanegra V, Benardon ME, Cacciamani V, Valles PG (2014) Hsp70 regulation on Nox4/p22phox and cytoskeletal integrity as an effect of losartan in vascular smooth muscle cells. Cell Stress Chaperones 19:115–134. https://doi.org/10.1007/s12192-013-0439-6
Gimbrone MA Jr, Garcia-Cardena G (2016) Endothelial cell dysfunction and the pathobiology of atherosclerosis. Circ Res 118:620–636. https://doi.org/10.1161/CIRCRESAHA.115.306301
Goettems-Fiorin PB et al (2016) Fine particulate matter potentiates type 2 diabetes development in high-fat diet-treated mice: stress response and extracellular to intracellular HSP70 ratio analysis. J Physiol Biochem 72:643–656. https://doi.org/10.1007/s13105-016-0503-7
Goettems-Fiorin PB et al (2019) Ovariectomy predisposes female rats to fine particulate matter exposure’s effects by altering metabolic, oxidative, pro-inflammatory, and heat-shock protein levels. Environ Sci Pollut Res Int. https://doi.org/10.1007/s11356-019-05383-9
Heck TG et al (2017) Acute exercise boosts cell proliferation and the heat shock response in lymphocytes: correlation with cytokine production and extracellular-to-intracellular HSP70 ratio. Cell Stress Chaperones 22:271–291. https://doi.org/10.1007/s12192-017-0771-3
Hemmingsen JG et al (2009) Prenatal exposure to diesel exhaust particles and effect on the male reproductive system in mice. Toxicology 264:61–68. https://doi.org/10.1016/j.tox.2009.07.012
Hou Y, Wei H, Luo Y, Liu G (2010) Modulating expression of brain heat shock proteins by estrogen in ovariectomized mice model of aging. Exp Gerontol 45:323–330. https://doi.org/10.1016/j.exger.2009.10.006
Kampfrath T et al (2011) Chronic fine particulate matter exposure induces systemic vascular dysfunction via NADPH oxidase and TLR4 pathways. Circ Res 108:716–726. https://doi.org/10.1161/CIRCRESAHA.110.237560
Kostrycki IM et al (2019) Effects of high-fat diet on eHSP72 and extra-to-intracellular HSP70 levels in mice submitted to exercise under exposure to fine particulate matter. J Diabetes Res 2019:4858740. https://doi.org/10.1155/2019/4858740
Krause M, Heck TG, Bittencourt A, Scomazzon SP, Newsholme P, Curi R, Homem de Bittencourt PI Jr (2015) The chaperone balance hypothesis: the importance of the extracellular to intracellular HSP70 ratio to inflammation-driven type 2 diabetes, the effect of exercise, and the implications for clinical management. Mediat Inflamm 2015:249205. https://doi.org/10.1155/2015/249205
Lima SMRRB-KA, Flues K, Paulin J, Monte O, Irigoyen MC, Angelis K (2007) Efeitos da suplementação do 17β-estradiol no dano oxidativo cardíaco de ratas submetidas à privação dos hormônios ovarianos. Rev Brasil Ginecol 29:27–33
Lima-Mendoza LA et al (2014) Vascular damage in obese female rats with hypoestrogenism. J Physiol Biochem 70:81–91. https://doi.org/10.1007/s13105-013-0283-2
Lissarassa YPS et al (2020) Chronic heat treatment positively impacts metabolic profile of ovariectomized rats: association with heat shock response pathways. Cell Stress Chaperones. https://doi.org/10.1007/s12192-020-01087-z
Liu, Gou, Zhang, Zuo, Zhang, Liu, Yao (2014) Estradiol improves cardiovascular function through up-regulation of SOD2 on vascular wall. Redox Biol 3:88–99. https://doi.org/10.1016/j.redox.2014.11.001
Ludwig MS, Minguetti-Camara VC, Heck TG, Scomazzon SP, Nunes PR, Bazotte RB, Homem de Bittencourt PI Jr (2014) Short-term but not long-term hypoglycaemia enhances plasma levels and hepatic expression of HSP72 in insulin-treated rats: an effect associated with increased IL-6 levels but not with IL-10 or TNF-alpha. Mol Cell Biochem 397:97–107. https://doi.org/10.1007/s11010-014-2176-2
Machi JF et al (2016) Impact of aging on cardiac function in a female rat model of menopause: role of autonomic control, inflammation, and oxidative stress. Clin Interv Aging 11:341–350. https://doi.org/10.2147/CIA.S88441
Mai AS et al (2017) Exercise training under exposure to low levels of fine particulate matter: effects on heart oxidative stress and extra-to-intracellular HSP70 ratio. Oxidative Med Cell Longev 2017:9067875. https://doi.org/10.1155/2017/9067875
Marchini T et al (2016) Acute exposure to air pollution particulate matter aggravates experimental myocardial infarction in mice by potentiating cytokine secretion from lung macrophages. Basic Res Cardiol 111:44. https://doi.org/10.1007/s00395-016-0562-5
Marklund S, Marklund G (1974) Involvement of the superoxide anion radical in the autoxidation of pyrogallol and a convenient assay for superoxide dismutase. Eur J Biochem 47:469–474
Medeiros N Jr et al (2004) Acute pulmonary and hematological effects of two types of particle surrogates are influenced by their elemental composition. Environ Res 95:62–70. https://doi.org/10.1016/j.envres.2003.07.007
Medina-Navarro R, Lifshitz A, Wacher N, Hicks JJ (1997) Changes in human serum antioxidant capacity and peroxidation after four months of exposure to air pollutants. Arch Med Res 28:205–208
Min W, Fang P, Huang G, Shi M, Zhang Z (2018) The decline of whole-body glucose metabolism in ovariectomized rats. Exp Gerontol 113:106–112. https://doi.org/10.1016/j.exger.2018.09.027
Minta W et al (2018) Estrogen deprivation aggravates cardiometabolic dysfunction in obese-insulin resistant rats through the impairment of cardiac mitochondrial dynamics. Exp Gerontol 103:107–114. https://doi.org/10.1016/j.exger.2018.01.006
Miragem AA, Homem de Bittencourt PI Jr (2017) Nitric oxide-heat shock protein axis in menopausal hot flushes: neglected metabolic issues of chronic inflammatory diseases associated with deranged heat shock response. Hum Reprod Update 23:600–628. https://doi.org/10.1093/humupd/dmx020
Miragem AAL, S M, Heck TG, Baldissera FG, Santos AB, Frizzo MN, Bittencourt PIH Jr (2015) Estrogen deprivation does not affect vascular heat shock response in female rats: a comparison with oxidative stress markers. Mol Cell Biochem 407:239–249. https://doi.org/10.1007/s11010-015-2472-5
Newsholme P, de Bittencourt PI Jr (2014) The fat cell senescence hypothesis: a mechanism responsible for abrogating the resolution of inflammation in chronic disease. Curr Opin Clin Nutri Metabol Care 17:295–305. https://doi.org/10.1097/MCO.0000000000000077
Niemann B, Rohrbach S, Miller MR, Newby DE, Fuster V, Kovacic JC (2017) Oxidative stress and cardiovascular risk: obesity, diabetes, smoking, and pollution: Part 3 of a 3-Part Series. J Am Coll Cardiol 70:230–251. https://doi.org/10.1016/j.jacc.2017.05.043
Perry JJ, Shin DS, Getzoff ED, Tainer JA (2010) The structural biochemistry of the superoxide dismutases. Biochim Biophys Acta 1804:245–262. https://doi.org/10.1016/j.bbapap.2009.11.004
Petisco AC et al (2017) High prevalence of subclinical atherosclerosis in Brazilian postmenopausal women with low and intermediate risk by Framingham score. Int J Card Imaging 33:401–410. https://doi.org/10.1007/s10554-016-1002-1
Proctor SD, Dreher KL, Kelly SE, Russell JC (2006) Hypersensitivity of prediabetic JCR:LA-cp rats to fine airborne combustion particle-induced direct and noradrenergic-mediated vascular contraction. Toxicol Sci 90:385–391. https://doi.org/10.1093/toxsci/kfj100
Radons J (2016) The human HSP70 family of chaperones: where do we stand? Cell Stress Chaperones 21:379–404. https://doi.org/10.1007/s12192-016-0676-6
Rangel-Zuniga OA et al (2017) Differential menopause-versus aging-induced changes in oxidative stress and circadian rhythm gene markers. Mech Ageing Dev 164:41–48. https://doi.org/10.1016/j.mad.2017.04.002
Saha JK, Xia J, Grondin JM, Engle SK, Jakubowski JA (2005) Acute hyperglycemia induced by ketamine/xylazine anesthesia in rats: mechanisms and implications for preclinical models. Exp Biol Med (Maywood) 230:777–784
Sancini G et al (2014) Health risk assessment for air pollutants: alterations in lung and cardiac gene expression in mice exposed to Milano winter fine particulate matter (PM2.5). PLoS One 9:e109685. https://doi.org/10.1371/journal.pone.0109685
Simon V et al (2017) Carbon black nanoparticles inhibit aromatase expression and estradiol secretion in human granulosa cells through the ERK1/2 Pathway. Endocrinology 158:3200–3211. https://doi.org/10.1210/en.2017-00374
Stice JP, Chen L, Kim SC, Jung JS, Tran AL, Liu TT, Knowlton AA (2011) 17beta-Estradiol, aging, inflammation, and the stress response in the female heart. Endocrinology 152:1589–1598. https://doi.org/10.1210/en.2010-0627
Taechakraichana N, Jaisamrarn U, Panyakhamlerd K, Chaikittisilpa S, Limpaphayom KK (2002) Climacteric: concept, consequence and care. J Med Assoc Thailand = Chotmaihet thangphaet 85(Suppl 1):S1–S15
WHO (2005) WHO-air quality guidelines–global update 2005. https://www.who.int/airpollution/publications/aqg2005/en/. October 27th, 2020
WHO (2020) WHO-cardiovascular diseases. https://www.who.int/health-topics/cardiovascular-diseases/#tab=tab_1. Accessed October 24th, 2020
Xie F, Zhan R, Yan LC, Gong JB, Zhao Y, Ma J, Qian LJ (2016) Diet-induced elevation of circulating HSP70 may trigger cell adhesion and promote the development of atherosclerosis in rats. Cell Stress Chaperones 21:907–914. https://doi.org/10.1007/s12192-016-0716-2
Yang Y et al (2019) Concentrated ambient PM2.5 exposure affects mice sperm quality and testosterone biosynthesis. Peer J 7:e8109. https://doi.org/10.7717/peerj.8109
Zhao H, Tian Z, Hao J, Chen B (2005) Extragonadal aromatization increases with time after ovariectomy in rats. Reprod Biol Endocrinol RB&E 3(6). https://doi.org/10.1186/1477-7827-3-6
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The authors would like to thank their colleagues from the Research Group in Physiology (UNIJUI).
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This study was supported by the Regional University of Northwestern Rio Grande do Sul State (UNIJUÍ). LCCB and GEH were recipients of scholarships from CAPES.
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LCCB, PBGF, JBS, and PTF completed all the experiment design described in this manuscript. LCCB evaluated the oxidative stress parameters and immunoblotting. LCCB, PBGF, JBS, PTF, and TGH performed the eHSP72 test. LCCB, PBGF, MSL, and TGH designed the study and provided experimental advice. LCCB did the statistical analysis, wrote the manuscript, and designed Fig. 1. PBGF, GEH, TGH, and MSL co-wrote this. All the authors had final approval of the submitted and published versions.
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This study followed all ethical rules established by Arouca’s Act (Federal Law 11,794/2008) and the Guide for Care and Use of Experimental Animals, published by the National Institutes of Health (NIH publication no. 85–23, revised in 1996). This protocol was approved by the Animal Ethics Committee of UNIJUÍ (CEUA-UNIJUÍ, protocol 076/15).
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Costa-Beber, L.C., Goettems-Fiorin, P.B., dos Santos, J.B. et al. Ovariectomy reduces the cardiac cytoprotection in rats exposed to particulate air pollutant. Environ Sci Pollut Res 28, 23395–23404 (2021). https://doi.org/10.1007/s11356-021-12350-w
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DOI: https://doi.org/10.1007/s11356-021-12350-w