nach oben

Cardiovascular Toxicology

Erschienen in:

20.05.2022

PM2.5-Induced Programmed Myocardial Cell Death via mPTP Opening Results in Deteriorated Cardiac Function in HFpEF Mice

verfasst von: Tingting Wu, Minghui Tong, Aiai Chu, Kaiyue Wu, Xiaowei Niu, Zheng Zhang

Erschienen in: Cardiovascular Toxicology | Ausgabe 8/2022

Einloggen, um Zugang zu erhalten

Abstract

PM2.5 exposure can induce or exacerbate heart failure and is associated with an increased risk of heart failure hospitalization and mortality; however, the underlying mechanisms remain unclear. This study focuses on the potential mechanisms underlying PM2.5 induction of cardiomyocyte programmed necrosis as well as its promotion of cardiac function impairment in a mouse model of heart failure with preserved ejection fraction (HFpEF). HFpEF mice were exposed to concentrated ambient PM2.5 (CAP) (CAP group) or filtered air (FA) (FA group) for 6 weeks. Changes in myocardial pathology and cardiac function were documented for comparisons between the two groups. In vitro experiments were performed to measure oxidative stress and mitochondrial permeability transition pore (mPTP) dynamics in H9C2 cells following 24 h exposure to PM2.5. Additionally, co-immunoprecipitation was conducted to detect p53 and cyclophilin D (CypD) interactions. The results showed exposure to CAP promoted cardiac function impairment in HFpEF mice. Myocardial pathology analysis and in vitro experiments demonstrated that PM2.5 led to mitochondrial damage in cardiomyocytes and, eventually, their necrosis. Moreover, our experiments also suggested that PM2.5 increases mitochondrial reactive oxygen species (ROS), induces DNA oxidative damage, and decreases the inner mitochondrial membrane potential (ΔΨm). This indicates the presence of mPTP opening. Co-immunoprecipitation results showed a p53/CypD interaction in the myocardial tissue of HFpEF mice in the CAP group. Inhibition of CypD by cyclosporin A was found to reverse PM2.5-induced mPTP opening and H9C2 cell death. In conclusion, PM2.5 induces mPTP opening to stimulate mitochondria-mediated programmed necrosis of cardiomyocytes, and it might exacerbate cardiac function impairment in HFpEF mice.

Nur mit Berechtigung zugänglich

GBD. (2017). Disease and Injury Incidence and Prevalence Collaborators. (2018). Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017:A systematic analysis for the Global Burden of Disease Study 2017. Lancet, 392, 1789–1858. https://doi.org/10.1016/S0140-6736(18)32279-7CrossRef

Groenewegen, A., Rutten, F. H., Mosterd, A., & Hoes, A. W. (2020). Epidemiology of heart failure. European Journal of Heart Failure, 22, 1342–1356.CrossRef

GBD. (2015). Risk Factors Collaborators. (2016). Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: A systematic analysis for the Global Burden of Disease Study 2015. Lancet, 388, 1659–1724. https://doi.org/10.1016/S0140-6736(16)31679-8CrossRef

Roth, G. A., Mensah, G. A., Johnson, C. O., Addolorato, G., Ammirati, E., Baddour, L. M., Barengo, N. C., Beaton, A. Z., Benjamin, E. J., Benziger, C. P., Bonny, A., Brauer, M., Brodmann, M., Cahill, T. J., Carapetis, J., Catapano, A. L., Chugh, S. S., Cooper, L. T., Coresh, J.,…, GBD-NHLBI-JACC Global Burden of Cardiovascular Diseases Writing Group. (2020). Global burden of cardiovascular diseases and risk factors, 1990–2019: Update from the GBD 2019 study. Journal of the American College of Cardiology, 76, 2982–3021.CrossRef

Rajagopalan, S., Al-Kindi, S. G., & Brook, R. D. (2018). Air pollution and cardiovascular disease: JACC state-of-the-art review. Journal of the American College of Cardiology, 72, 2054–2070.CrossRef

Shah, A. S., Langrish, J. P., Nair, H., McAllister, D. A., Hunter, A. L., Donaldson, K., Newby, D. E., & Mills, N. L. (2013). Global association of air pollution and heart failure: A systematic review and meta-analysis. Lancet, 382, 1039–1048.CrossRef

Dominici, F., Peng, R. D., Bell, M. L., Pham, L., McDermott, A., Zeger, S. L., & Samet, J. M. (2006). Fine particulate air pollution and hospital admission for cardiovascular and respiratory diseases. JAMA, 295, 1127–1134.CrossRef

Borlaug, B. A., & Redfield, M. M. (2011). Diastolic and systolic heart failure are distinct phenotypes within the heart failure spectrum. Circulation, 123, 2006–2013.CrossRef

Ponikowski, P., Voors, A. A., Anker, S. D., Bueno, H., Cleland, J. G., Coats, A. J., Falk, V., González-Juanatey, J. R., Harjola, V. P., Jankowska, E. A., Jessup, M., Linde, C., Nihoyannopoulos, P., Parissis, J. T., Pieske, B., Riley, J. P., Rosano, G. M., Ruilope, L. M., & Ruschitzka, F.,…, Document Reviewers. (2016). 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. European Journal of Heart Failure, 18, 891–975.CrossRef

10.

Bursi, F., Weston, S. A., Redfield, M. M., Jacobsen, S. J., Pakhomov, S., Nkomo, V. T., Meverden, R. A., & Roger, V. L. (2006). Systolic and diastolic heart failure in the community. JAMA, 296, 2209–2216.CrossRef

11.

Roy, A., Gong, J., Thomas, D. C., Zhang, J., Kipen, H. M., Rich, D. Q., Zhu, T., Huang, W., Hu, M., Wang, G., Wang, Y., Zhu, P., Lu, S. E., Ohman-Strickland, P., Diehl, S. R., & Eckel, S. P. (2014). The cardiopulmonary effects of ambient air pollution and mechanistic pathways: A comparative hierarchical pathway analysis. PLoS ONE, 9, e114913.CrossRef

12.

Andreyev, A. Y., Kushnareva, Y. E., & Starkov, A. A. (2005). Mitochondrial metabolism of reactive oxygen species. Biochemistry, 70, 200–214. https://doi.org/10.1007/s10541-005-0102-7CrossRefPubMed

13.

Kuznetsov, A. V., Javadov, S., Grimm, M., Margreiter, R., Ausserlechner, M. J., & Hagenbuchner, J. (2020). Crosstalk between mitochondria and cytoskeleton in cardiac cells. Cells, 9, 222.CrossRef

14.

Yang, X., Zhao, T., Feng, L., Shi, Y., Jiang, J., Liang, S., Sun, B., Xu, Q., Duan, J., & Sun, Z. (2019). PM 2.5-induced ADRB2 hypermethylation contributed to cardiac dysfunction through cardiomyocytes apoptosis via PI3K/Akt pathway. Environment International, 127, 601–614.CrossRef

15.

Yang, X., Feng, L., Zhang, Y., Hu, H., Shi, Y., Liang, S., Zhao, T., Fu, Y., Duan, J., & Sun, Z. (2018). Cytotoxicity induced by fine particulate matter (PM 2.5) via mitochondria-mediated apoptosis pathway in human cardiomyocytes. Ecotoxicology and Environmental Safety, 161, 198–207.CrossRef

16.

Del, Re., & D. P., Amgalan, D., Linkermann, A., Liu, Q., & Kitsis, R. N. (2019). Fundamental mechanisms of regulated cell death and implications for heart disease. Physiological Reviews, 99, 1765–1817.CrossRef

17.

Bernardi, P. (2018). Why F-ATP synthase remains a strong candidate as the mitochondrial permeability transition pore. Frontiers in Physiology, 9, 1543. https://doi.org/10.3389/fphys.2018.01543CrossRefPubMedPubMedCentral

18.

Kwong, J. Q., & Molkentin, J. D. (2015). Physiological and pathological roles of the mitochondrial permeability transition pore in the heart. Cell Metabolism, 21, 206–214.CrossRef

19.

Baines, C. P., Song, C. X., Zheng, Y. T., Wang, G. W., Zhang, J., Wang, O. L., Guo, Y., Bolli, R., Cardwell, E. M., & Ping, P. (2003). Protein kinase Cepsilon interacts with and inhibits the permeability transition pore in cardiac mitochondria. Circulation Research, 92, 873–880. https://doi.org/10.1161/01.RES.0000069215.36389.8DCrossRefPubMedPubMedCentral

20.

Karch, J., Kwong, J. Q., Burr, A. R., Sargent, M. A., Elrod, J. W., Peixoto, P. M., Martinez-Caballero, S., Osinska, H., Cheng, E. H., Robbins, J., Kinnally, K. W., & Molkentin, J. D. (2013). Bax and Bak function as the outer membrane component of the mitochondrial permeability pore in regulating necrotic cell death in mice. eLife, 2, e00772. https://doi.org/10.7554/eLife.00772.002CrossRefPubMedPubMedCentral

21.

Holland, N. A., Fraiser, C. R., Sloan, R. C., Devlin, R. B., Brown, D. A., & Wingard, C. J. (2017). Ultrafine particulate matter increases cardiac ischemia/reperfusion injury via mitochondrial permeability transition pore. Cardiovascular Toxicology, 17, 441–450. https://doi.org/10.1007/s12012-017-9402-6CrossRefPubMedPubMedCentral

22.

Carbone, L. (2012). Pain management standards in the guide for the care and use of laboratory animals. Journal of the American Association for Laboratory Animal Science, 51, 322–328.PubMedPubMedCentral

23.

Schiattarella, G. G., Altamirano, F., Tong, D., French, K. M., Villalobos, E., Kim, S. Y., Luo, X., Jiang, N., May, H. I., Wang, Z. V., Hill, T. M., Mammen, P. P. A., Huang, J., Lee, D. I., Hahn, V. S., Sharma, K., Kass, D. A., Lavandero, S., Gillette, T. G., & Hill, J. A. (2019). Nitrosative stress drives heart failure with preserved ejection fraction. Nature, 568, 351–356.CrossRef

24.

Geller, M. D., Biswas, S., Fine, P. M., & Sioutas, C. (2005). A new compact aerosol concentrator for use in conjunction with low flow-rate continuous aerosol instrumentation. Journal of Aerosol Science, 36, 1006–1022. https://doi.org/10.1016/j.jaerosci.2004.11.015CrossRef

25.

Maciejczyk, P., Zhong, M., Li, Q., Xiong, J., Nadziejko, C., & Chen, L. C. (2005). Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice: II. The design of a CAPs exposure system for biometric telemetry monitoring. Inhalation Toxicology, 17, 189–197. https://doi.org/10.1080/08958370590912743CrossRefPubMed

26.

Feng, L., Wei, J., Liang, S., Sun, Z., & Duan, J. (2020). miR-205/IRAK2 signaling pathway is associated with urban airborne PM 2.5-induced myocardial toxicity. Nanotoxicology, 14, 1198–1212.CrossRef

27.

Petronilli, V., Miotto, G., Canton, M., Colonna, R., Bernardi, P., Di, L., & F. (1998). Imaging the mitochondrial permeability transition pore in intact cells. BioFactors, 8, 263–272. https://doi.org/10.1002/biof.5520080314CrossRefPubMed

28.

NavaneethaKrishnan, S., Rosales, J. L., & Lee, K. Y. (2020). mPTP opening caused by Cdk5 loss is due to increased mitochondrial Ca2+ uptake. Oncogene, 39, 2797–2806. https://doi.org/10.1038/s41388-020-1188-5CrossRefPubMedPubMedCentral

29.

Brook, R. D., Rajagopalan, S., Pope, C. A., 3rd., Brook, J. R., Bhatnagar, A., Diez-Roux, A. V., Holguin, F., Hong, Y., Luepker, R. V., Mittleman, M. A., Peters, A., Siscovick, D., Smith, S. C., Jr., Whitsel, L., Kaufman, J. D., Council, A. H. A., & on Epidemiology and Prevention, Council on the Kidney in Cardiovascular Disease, & Council on Nutrition, Physical Activity and Metabolism. (2010). Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation, 121, 2331–2378.CrossRef

30.

Yue, W., Tong, L., Liu, X., Weng, X., Chen, X., Wang, D., Dudley, S. C., Weir, E. K., Ding, W., Lu, Z., Xu, Y., & Chen, Y. (2019). Short term PM2.5 exposure caused a robust lung inflammation, vascular remodeling, and exacerbated transition from left ventricular failure to right ventricular hypertrophy. Redox Biology, 22, 101161.CrossRef

31.

Vaseva, A. V., Marchenko, N. D., Ji, K., Tsirka, S. E., Holzmann, S., & Moll, U. M. (2012). p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell, 149, 1536–1548. https://doi.org/10.1016/j.cell.2012.05.014CrossRefPubMedPubMedCentral

32.

Williams, A. B., & Schumacher, B. (2016). p53 in the DNA-damage-repair process. Cold Spring Harbor Perspectives in medicine, 6, a026070.CrossRef

33.

Pope, C. A., 3rd., Burnett, R. T., Thurston, G. D., Thun, M. J., Calle, E. E., Krewski, D., & Godleski, J. J. (2004). Cardiovascular mortality and long-term exposure to particulate air pollution: Epidemiological evidence of general pathophysiological pathways of disease. Circulation, 109, 71–77.CrossRef

34.

Miller, M. R., & Newby, D. E. (2020). Air pollution and cardiovascular disease: Car sick. Cardiovascular Research, 116, 279–294. https://doi.org/10.1093/cvr/cvz228CrossRefPubMed

35.

Cosselman, K. E., Navas-Acien, A., & Kaufman, J. D. (2015). Environmental factors in cardiovascular disease. Nature Reviews. Cardiology, 12, 627–642. https://doi.org/10.1038/nrcardio.2015.152CrossRefPubMed

36.

Seaton, A., MacNee, W., Donaldson, K., & Godden, D. (1995). Particulate air pollution and acute health effects. Lancet, 345, 176–178. https://doi.org/10.1016/S0140-6736(95)90173-6CrossRefPubMed

37.

Perez, C. M., Hazari, M. S., & Farraj, A. K. (2015). Role of autonomic reflex arcs in cardiovascular responses to air pollution exposure. Cardiovascular Toxicology, 15, 69–78. https://doi.org/10.1007/s12012-014-9272-0CrossRefPubMedPubMedCentral

38.

Pope, C. A., 3rd., Verrier, R. L., Lovett, E. G., Larson, A. C., Raizenne, M. E., Kanner, R. E., Schwartz, J., Villegas, G. M., Gold, D. R., & Dockery, D. W. (1999). Heart rate variability associated with particulate air pollution. American Heart Journal, 138, 890–899. https://doi.org/10.1016/s0002-8703(99)70014-1CrossRefPubMed

39.

Kodavanti, U. P. (2016). Stretching the stress boundary: Linking air pollution health effects to a neurohormonal stress response. Biochimica et Biophysica Acta, 1860, 2880–2890. https://doi.org/10.1016/j.bbagen.2016.05.010CrossRefPubMed

40.

Wallenborn, J. G., McGee, J. K., Schladweiler, M. C., Ledbetter, A. D., & Kodavanti, U. P. (2007). Systemic translocation of particulate matter-associated metals following a single intratracheal instillation in rats. Toxicological Sciences, 98, 231–239. https://doi.org/10.1093/toxsci/kfm088CrossRefPubMed

41.

Cui, L., Shi, L., Li, D., Li, X., Su, X., Chen, L., Jiang, Q., Jiang, M., Luo, J., Ji, A., Chen, C., Wang, J., Tang, J., Pi, J., Chen, R., Chen, W., Zhang, R., & Zheng, Y. (2020). Real-ambient particulate matter exposure-induced cardiotoxicity in C57/inB6 mice. Frontiers in Pharmacology, 11, 199. https://doi.org/10.3389/fphar.2020.00199CrossRefPubMedPubMedCentral

42.

Nakane, H. (2012). Translocation of particles deposited in the respiratory system: A systematic review and statistical analysis. Environmental Health and Preventive Medicine, 17, 263–274. https://doi.org/10.1007/s12199-011-0252-8CrossRefPubMed

43.

Hamanaka, R. B., & Mutlu, G. M. (2018). Particulate matter air pollution: Effects on the cardiovascular system. Frontiers in Endocrinology, 9, 680.CrossRef

44.

Zuo, L., Youtz, D. J., & Wold, L. E. (2011). Particulate matter exposure exacerbates high glucose-induced cardiomyocyte dysfunction through ROS generation. PLoS ONE, 6, e23116.CrossRef

45.

Danial, N. N., & Korsmeyer, S. J. (2004). Cell death: Critical control points. Cell, 116, 205–219.CrossRef

46.

Van, der, Pol, A., Van, Gilst, W.H., Voors, A.A., Van, der, & Meer, P. (2019). Treating oxidative stress in heart failure: Past, present and future. European Journal of Heart Failure, 21, 425–435. https://doi.org/10.1002/ejhf.1320CrossRef

47.

Karimi, G. K., Antoniades, C., Nicholls, S. J., Channon, K. M., & Figtree, G. A. (2015). Redox biomarkers in cardiovascular medicine. European Heart Journal, 36, 1576–1582.CrossRef

48.

Forkink, M., Basit, F., Teixeira, J., Swarts, H. G., Koopman, W. J. H., & Willems, P. H. G. M. (2015). Complex I and complex III inhibition specifically increase cytosolic hydrogen peroxide levels without inducing oxidative stress in HEK293 cells. Redox Biology, 6, 607–616.CrossRef

49.

Zorov, D. B., Filburn, C. R., Klotz, L. O., Zweier, J. L., & Sollott, S. J. (2000). Reactive oxygen species (ROS)-induced ROS release: A new phenomenon accompanying induction of the mitochondrial permeability transition in cardiac myocytes. The Journal of Experimental Medicine, 192, 1001–1014.CrossRef

50.

Fang, E. F., Scheibye-Knudsen, M., Chua, K. F., Mattson, M. P., Croteau, D. L., & Bohr, V. A. (2016). Nuclear DNA damage signalling to mitochondria in ageing. Nature Reviews, 17, 308–321.CrossRef

51.

Lesnefsky, E. J., Moghaddas, S., Tandler, B., Kerner, J., & Hoppel, C. L. (2001). Mitochondrial dysfunction in cardiac disease: Ischemia–reperfusion, aging, and heart failure. Journal of Molecular and Cellular Cardiology, 33, 1065–1089.CrossRef

52.

Halestrap, A. P. (2009). What is the mitochondrial permeability transition pore? Journal of Molecular and Cellular Cardiology, 46, 821–831.CrossRef

53.

Riemann, A., Schneider, B., Ihling, A., Nowak, M., Sauvant, C., Thews, O., & Gekle, M. (2011). Acidic environment leads to ROS-induced MAPK signaling in cancer cells. PLoS ONE, 6, e22445.CrossRef

54.

Carll, A. P., Haykal-Coates, N., Winsett, D. W., Rowan, W. H., 3rd., Hazari, M. S., Ledbetter, A. D., Nyska, A., Cascio, W. E., Watkinson, W. P., Costa, D. L., & Farraj, A. K. (2010). Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy. Inhalation Toxicology, 22, 355–368. https://doi.org/10.3109/08958370903365692CrossRefPubMed

55.

Carll, A. P., Lust, R. M., Hazari, M. S., Perez, C. M., Krantz, Q. T., King, C. J., Winsett, D. W., Cascio, W. E., Costa, D. L., & Farraj, A. K. (2013). Diesel exhaust inhalation increases cardiac output, bradyarrhythmias, and parasympathetic tone in aged heart failure-prone rats. Toxicological Sciences, 131, 583–595. https://doi.org/10.1093/toxsci/kfs295CrossRefPubMed

56.

Carll, A. P., Hazari, M. S., Perez, C. M., Krantz, Q. T., King, C. J., Haykal-Coates, N., Cascio, W. E., Costa, D. L., & Farraj, A. K. (2013). An autonomic link between inhaled diesel exhaust and impaired cardiac performance: Insight from treadmill and dobutamine challenges in heart failure-prone rats. Toxicological Sciences, 135, 425–436. https://doi.org/10.1093/toxsci/kft155CrossRefPubMedPubMedCentral

57.

Carll, A. P., Hazari, M. S., Perez, C. M., Krantz, Q. T., King, C. J., Winsett, D. W., Costa, D. L., & Farraj, A. K. (2012). Whole and particle-free diesel exhausts differentially affect cardiac electrophysiology, blood pressure, and autonomic balance in heart failure-prone rats. Toxicological Sciences, 128, 490–499. https://doi.org/10.1093/toxsci/kfs162CrossRefPubMedPubMedCentral

58.

Carll, A. P., Haykal-Coates, N., Winsett, D. W., Hazari, M. S., Ledbetter, A. D., Richards, J. H., Cascio, W. E., Costa, D. L., & Farraj, A. K. (2015). Cardiomyopathy confers susceptibility to particulate matter-induced oxidative stress, vagal dominance, arrhythmia and pulmonary inflammation in heart failure-prone rats. Inhalation Toxicology, 27, 100–112. https://doi.org/10.3109/08958378.2014.995387CrossRefPubMedPubMedCentral

59.

Carll, A. P., Crespo, S. M., Filho, M. S., Zati, D. H., Coull, B. A., Diaz, E. A., Raimundo, R. D., Jaeger, T. N. G., Ricci-Vitor, A. L., Papapostolou, V., Lawrence, J. E., Garner, D. M., Perry, B. S., Harkema, J. R., & Godleski, J. J. (2017). Inhaled ambient-level traffic-derived particulates decrease cardiac vagal influence and baroreflexes and increase arrhythmia in a rat model of metabolic syndrome. Particle and Fibre Toxicology, 14, 16. https://doi.org/10.1186/s12989-017-0196-2CrossRefPubMedPubMedCentral

Titel: PM2.5-Induced Programmed Myocardial Cell Death via mPTP Opening Results in Deteriorated Cardiac Function in HFpEF Mice
verfasst von: Tingting Wu
Minghui Tong
Aiai Chu
Kaiyue Wu
Xiaowei Niu
Zheng Zhang
Publikationsdatum: 20.05.2022
Verlag: Springer US
Erschienen in: Cardiovascular Toxicology / Ausgabe 8/2022
Print ISSN: 1530-7905
Elektronische ISSN: 1559-0259
DOI: https://doi.org/10.1007/s12012-022-09753-7

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 8/2022

Impact of DYRK1A Expression on TNNT2 Splicing and Daunorubicin Toxicity in Human iPSC-Derived Cardiomyocytes

Hesperidin Attenuates Oxidative Stress, Inflammation, Apoptosis, and Cardiac Dysfunction in Sodium Fluoride‐Induced Cardiotoxicity in Rats

Improved Cardiac Function Following Ischemia Reperfusion Injury Using Exercise Preconditioning and L-Arginine Supplementation via Oxidative Stress Mitigation and Angiogenesis Amelioration

Asthma can Promote Cardiomyocyte Mitophagy in a Rat Model

Bone Marrow Mesenchymal Stem Cell-Derived Exosomal microRNA-29b-3p Promotes Angiogenesis and Ventricular Remodeling in Rats with Myocardial Infarction by Targeting ADAMTS16

Titanium Dioxide (E171) Induces Toxicity in H9c2 Rat Cardiomyoblasts and Ex Vivo Rat Hearts