Electroacupuncture alleviates myocardial ischemia-reperfusion injury by inhibiting hypothalamic paraventricular nucleus neurons projecting to the rostral ventrolateral medulla.

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      Publisher: Wiley-Blackwell Country of Publication: France NLM ID: 8918110 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1460-9568 (Electronic) Linking ISSN: 0953816X NLM ISO Abbreviation: Eur J Neurosci Subsets: MEDLINE
    • Publication Information:
      Publication: : Oxford : Wiley-Blackwell
      Original Publication: Oxford, UK : Published on behalf of the European Neuroscience Association by Oxford University Press, c1989-
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    • Abstract:
      Accumulating evidence suggests that electroacupuncture (EA) has obvious therapeutic effects and unique advantages in alleviating myocardial ischemia-reperfusion injury (MIRI), while the underlying neuromolecular mechanisms of EA intervention for MIRI have not been fully elucidated. The aim of the study is to investigate the role of the neural pathway of hypothalamic paraventricular nucleus (PVN) neurons projecting to the rostral ventrolateral medulla (RVLM) in the alleviation of MIRI rats by EA preconditioning. MIRI models were established by ligating the left anterior descending coronary artery for 30 min followed by reperfusion for 2 h. Electrocardiogram recording, chemogenetics, enzyme-linked immunosorbent assay, multichannel physiology recording and haematoxylin-eosin and immunofluorescence staining methods were conducted to demonstrate that the firing frequencies of neurons in the PVN and the expression of c-Fos decreased by EA pretreatment. Meanwhile, EA preconditioning significantly reduced the levels of creatine kinase isoenzymes (CK-MB), cardiac troponin I (cTnI) and lactic dehydrogenase (LDH). Virus tracing showed a projection connection between PVN and RVLM. The inhibition of the PVN-RVLM neural pathway could replicate the protective effect of EA pretreatment on MIRI rats. However, the activation of the pathway weakened the effect of EA preconditioning. EA pretreatment alleviated MIRI by regulating PVN neurons projecting to RVLM. This work provides novel evidence of EA pretreatment for alleviating MIRI.
      (© 2024 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.)
    • References:
      Allen, D. G., & Orchard, C. H. (1987). Myocardial contractile function during ischemia and hypoxia. Circulation Research, 60(2), 153–168. https://doi.org/10.1161/01.RES.60.2.153.
      Bai, H., Xu, S. L., Shi, J.‐J., Ding, Y. P., Liu, Q. Q., Jiang, C. H., He, L. L., Zhang, H. R., Lu, S. F., & Gu, Y. H. (2023). Electroacupuncture preconditioning protects against myocardial ischemia‐reperfusion injury by modulating dynamic inflammatory response. Heliyon, 9, e19396. https://doi.org/10.1016/j.heliyon.2023.e19396.
      Bugger, H., & Pfeil, K. (2020). Mitochondrial ROS in myocardial ischemia reperfusion and remodeling. Biochimica et Biophysica Acta ‐ Molecular Basis of Disease, 1866(7), 165768. https://doi.org/10.1016/j.bbadis.2020.165768.
      Bullitt, E. (1990). Expression of c‐fos like protein as a marker for neuronal activity following noxious stimulation in the rat. The Journal of Comparative Neurology, 296(4), 517–530. https://doi.org/10.1002/cne.902960402.
      Charkoudian, N., & Wallin, B. G. (2014). Sympathetic neural activity to the cardiovascular system: Integrator of systemic physiology and interindividual characteristics. Comprehensive Physiology, 4(2), 825–850. https://doi.org/10.1002/cphy.c130038.
      Chen, C., Zhu, X.‐y., Zhou, K., Li, D., & Lin, Q. (2020). Cardioprotective effect of acupuncture for percutaneous coronary intervention‐related myocardial injury in patients with coronary artery disease. Medicine, 99(20), e20135. https://doi.org/10.1097/MD.0000000000020135.
      Chen, Q. H., Haywood, J. R., & Toney, G. M. (2003). Sympathoexcitation by PVN‐injected bicuculline requires activation of excitatory amino acid receptors. Hypertension, 42(4), 725–731. https://doi.org/10.1161/01.HYP.0000085197.20043.44.
      Chen, Z. H., Xue, B., Li, S. J., Liu, C. J., Ren, H., & Ren, Y. L. (2020). Research status and prospects on adenosine receptor mechanism of acupuncture for myocardial ischemia. Zhongguo Zhen Jiu = Chinese Acupuncture & Moxibustion, 40(11), 1265–1270.
      Cheng, W., Sun, Y., Wu, Q., Ooi, K., Feng, Y., Xia, C., & Zhu, D. (2021). Paraventricular nucleus P2X7 receptors aggravate acute myocardial infarction injury via ROS‐induced vasopressin‐V1b activation in rats. Neuroscience Bulletin, 37(5), 641–656. https://doi.org/10.1007/s12264-021-00641-8.
      Dampney, R. A. L. (1994). Functional organization of central pathways regulating the cardiovascular system. Physiological Reviews, 74(2), 323–364.
      Danson, E. J. F., & Paterson, D. J. (2006). Reactive oxygen species and autonomic regulation of cardiac excitability. Journal of Cardiovascular Electrophysiology, 17, 104–112.
      de Lima Pimentel, R., Duque, A. P., Moreira, B. R., & Junior, L. F. (2019). Acupuncture for the treatment of cardiovascular diseases: A systematic review. Journal of Acupuncture and Meridian Studies, 12(2), 43–51.
      Feng, X.‐F., Hai, J. J., Ma, Y., Wang, Z. Q., & Tse, H. F. (2018). Sudden cardiac death in mainland China: A systematic analysis. Circulation. Arrhythmia and Electrophysiology, 11(11), e006684. https://doi.org/10.1161/CIRCEP.118.006684.
      Guyenet, P. G. (2006). The sympathetic control of blood pressure. Nature Reviews. Neuroscience, 7(5), 335–346. https://doi.org/10.1038/nrn1902.
      Jennings, R. B. (2013). Historical perspective on the pathology of myocardial ischemia/reperfusion injury. Circulation Research, 113(4), 428–438. https://doi.org/10.1161/CIRCRESAHA.113.300987.
      Kalogeris, T., Baines, C. P., Krenz, M., & Korthuis, R. J. (2016). Ischemia/reperfusion. Comprehensive Physiology, 7(1), 113–170. https://doi.org/10.1002/cphy.c160006.
      Koba, S., Hanai, E., Kumada, N., Kataoka, N., Nakamura, K., & Watanabe, T. (2018). Sympathoexcitation by hypothalamic paraventricular nucleus neurons projecting to the rosral ventrolateral medulla. The Journal of Physiology, 596(19), 4581–4595. https://doi.org/10.1113/JP276223.
      Lam, L., Ha, L., Gladding, P., Tse, R., & Kyle, C. (2021). Effect of macrotroponin on the utility of cardiac troponin I as a prognostic biomarker for long term total and cardiovascular disease mortality. Pathology, 53(7), 860–866. https://doi.org/10.1016/j.pathol.2021.04.005.
      Li, R. Q., Wan, L., Zi, M. J., Duan, W. H., He, L. Y., & Gao, R. R. (2022). Stable angina pectoris of coronary heart disease treated with different acupuncture and moxibustion therapies: A network meta‐analysis. Zhongguo Zhen Jiu, 42(12), 1431–1438. https://doi.org/10.13703/j.0255-2930.20220513-0002.
      Li, Y., Barajas‐Martinez, H., Li, B., Gao, Y., Zhang, Z., Shang, H., Xing, Y., & Hu, D. (2017). Comparative effectiveness of acupuncture and antiarrhythmic drugs for the prevention of cardiac arrhythmias: A systematic review and meta‐analysis of randomized controlled trials. Frontiers in Physiology, 8, 358. https://doi.org/10.3389/fphys.2017.00358.
      Liu, Y., Meng, H. Y., Khurwolah, M. R., Liu, J. B., Tang, H., Aa, N., & Yang, Z. J. (2019). Acupuncture therapy for the treatment of stable angina pectoris: An updated meta‐analysis of randomized controlled trials. Complementary Therapies in Clinical Practice, 34, 247–253. https://doi.org/10.1016/j.ctcp.2018.12.012.
      Ma, P., Dong, X., Qu, Y., He, Z., Yin, T., Cheng, S., Tian, Z., Teng, Y., Xie, K., Sun, R., Yu, S., & Zeng, F. (2021). A narrative review of neuroimaging studies in acupuncture for migraine. Pain Research and Management, 2021, 9460695. https://doi.org/10.1155/2021/9460695.
      Malliani, A., & Montano, N. (2002). Emerging excitatory role of cardiovascular sympathetic afferents in pathophysiological conditions. Hypertension, 39(1), 63–68. https://doi.org/10.1161/hy0102.099200.
      McHugh, N. A., Cook, S. M., Schairer, J. L., Bidgoli, M. M., & Merrill, G. F. (1995). Ischemia‐ and reperfusion‐induced ventricular arrhythmias in dogs: Effects of estrogen. The American Journal of Physiology, 268(6 Pt 2), 2569–2573.
      Meng, X., Gao, W. Q., & Sun, Z. (2019). Amiodarone and acupuncture for cardiac arrhythmia: Study protocol for a systematic review. Medicine (Baltimore), 98(7), e14544. https://doi.org/10.1097/MD.0000000000014544.
      Mensah, G. A., Roth, G. A., & Fuster, V. (2019). The global burden of cardiovascular diseases and risk factors: 2020 and beyond. Journal of the American College of Cardiology, 74(20), 2529–2532. https://doi.org/10.1016/j.jacc.2019.10.009.
      Mueller, P. J., Cunningham, J. T., Patel, K. P., & Hasser, E. M. (2003). Proposed role of the paraventricular nucleus in cardiovascular deconditioning. Acta Physiologica Scandinavica, 177(1), 27–35. https://doi.org/10.1046/j.1365-201X.2003.01044.x.
      Nishihara, M., Takesue, K., & Hirooka, Y. (2017). Renal denervation enhances GABA‐ergic input into the PVN leading to blood pressure lowering in chronic kidney disease. Autonomic Neuroscience, 204, 88–97. https://doi.org/10.1016/j.autneu.2016.09.018.
      Pruvot, E., Thonet, G., Vesin, J. M., van‐Melle, G., Seidl, K., Schmidinger, H., Brachmann, J., Jung, W., Hoffmann, E., Tavernier, R., Block, M., Podczeck, A., & Fromer, M. (2000). Heart rate dynamics at the onset of ventricular tachyarrhythmias as retrieved from implantable cardioverter‐defibrillators in patients with coronary artery disease. Circulation, 101, 2398–2404. https://doi.org/10.1161/01.CIR.101.20.2398.
      Ríha, H., Neckář, J., Papoušek, F., Netuka, I., Pirk, J., Kolář, F., & Ošťádal, B. (2011). Suppression of ischemic and reperfusion ventricular arrhythmias by inhalational anesthetic‐induced preconditioning in the rat heart. Physiological Research, 60(4), 709–714. https://doi.org/10.33549/physiolres.932137.
      Ronglin, C. (2018). Effect of electroacupuncture on the electrical activity of neurons in the hypothalamic paraventricular nucleus in rats with myocardial ischemia. Acupuncture Research, 43(7), 406–413.
      Rossi, N. F., Maliszewska‐Scislo, M., Chen, H., Black, S. M., Sharma, S., Ravikov, R., & Augustyniak, R. A. (2010). Neuronal nitric oxide synthase within paraventricular nucleus: Blood pressure and baroreflex in two‐kidney, one‐clip hypertensive rats. Experimental Physiology, 95(8), 845–857. https://doi.org/10.1113/expphysiol.2009.051789.
      Schwartz, P. J. (2014). Cardiac sympathetic denervation to prevent life‐threatening arrhythmias. Nature Reviews. Cardiology, 11(6), 346–353. https://doi.org/10.1038/nrcardio.2014.19.
      Shafton, A. D., Ryan, A., & Badoer, E. (1998). Neurons in the hypothalamic paraventricular nucleus send collaterals to the spinal cord and to the rostral ventrolateral medulla in the rat. Brain Research, 801, 239–243. https://doi.org/10.1016/s0006-8993(98)00587-3.
      Shan, Y., Wang, Z. Q., Zhao, Z. L., Zhang, M., Hao, S. L., Xu, J. Y., Shan, B. C., Lu, J., & Li, K. C. (2014). An FMRI study of neuronal specificity in acupuncture: The multiacupoint siguan and its sham point. Evidence‐Based Complementary and Alternative Medicine, 2014, 103491.
      Shi, Y., Yin, J., Hu, H., Xue, M., Li, X., Liu, J., Li, Y., Cheng, W., Wang, Y., Li, X., Wang, Y., Liu, F., Liu, Q., Tan, J., & Yan, S. (2019). Targeted regulation of sympathetic activity in paraventricular nucleus reduces inducible ventricular arrhythmias in rats after myocardial infarction. Journal of Cardiology, 73, 81–88. https://doi.org/10.1016/j.jjcc.2018.06.003.
      Tjen‐A‐Looi, S. C., Guo, Z. L., Fu, L. W., & Longhurst, J. C. (2016). Paraventricular nucleus modulates excitatory cardiovascular reflexes during electroacupuncture. Scientific Reports, 6(1), 25910.
      Wang, K., You, S., Hu, H., Li, X., Yin, J., Shi, Y., Qi, L., Li, P., Zhao, Y., & Yan, S. (2022). Effect of TLR4/MyD88/NF‐kB axis in paraventricular nucleus on ventricular arrhythmias induced by sympathetic hyperexcitation in post‐myocardial infarction rats. Journal of Cellular and Molecular Medicine, 26(10), 1–13. https://doi.org/10.1111/jcmm.17309.
      Wang, S. Y., Shu, Q., Chen, P. P., Zhang, F., Zhou, X., Wang, Q. Y., Zhou, J., Wei, X., Hu, L., Yu, Q., & Cai, R. L. (2023). Effects of electroacupuncture pretreatment on GABAA receptor of fastigial nucleus and sympathetic nerve activity in rats with myocardial ischemia reperfusion injury. Zhonguo Zhen Jiu, 43(6), 669–678.
      Wang, Y., Xuan, Y. L., Hu, H. S., Li, X. L., Xue, M., Cheng, W. J., Suo, F., & Yan, S. H. (2012). Risk of ventricular arrhythmias after myocardial infarction with diabetes associated with sympathetic neural remodeling in rabbits. Cardiology, 121(1), 1–9. https://doi.org/10.1159/000336148.
      Wei, X., Liaoyuan, L. I., Zhang, Y., Qi, S. H., Shuaiya, W. A., Pianpian, C. H., Ling, H. U., Qing, Y. U., & Ronglin, C. A. (2022). Electroacupuncture preconditionng alleviates myocardial ischemia‐reperfusion injury through the hypothalamic paraventricular nucleus‐interposed nucleus nerve pathway. Journal of Traditional Chinese Medicine, 42(3), 379–388.
      Weixing, P. (2018). Neurobiological mechanism of acupuncture and moxibustion. Chinese Journal of Traditional Chinese Medicine, 33(10), 4281–4297.
      Wenwen, W., Qiongbo, W. U., Zheng, C., Mengya, W. A., & Zhang, H. (2020). Neural pathway between the nucleus accumbens and the rostral ventrolateral medulla in a rat model of anorexia nervosa. Journal of Southern Medical University, 40(5), 609–615.
      Wit, A. L., & Janse, M. J. (2001). Reperfusion arrhythmias and sudden cardiac death: A century of progress toward an understanding of the mechanisms. Circulation Research, 89(9), 741–743. https://doi.org/10.1161/res.89.9.741.
      Xia, X. F., Liu, Y. C., Lu, S. F., Bai, H., Xu, S. L., Sun, K., Wu, J. H., Gu, Y. H., & Zhang, H. R. (2022). Effect of electroacupuncture preconditioning on expression of Gasdermin D, Caspase‐1 and IL‐1β in rats with myocardial ischemia reperfusion injury. Zhen Ci Yan Jiu, 47(5), 443–448. https://doi.org/10.13702/j.1000-0607.20210286.
      Xu, B., Zheng, H., & Patel, K. P. (2012). Enhanced activation of RVLM‐projecting PVN neurons in rats with chronic heart failure. American Journal of Physiology ‐ Heart and Circulatory Physiology, 302(8), 700–711. https://doi.org/10.1152/ajpheart.00722.2011.
      Xu, W., Zhang, L., Zhang, Y., Zhang, K., Wu, Y., & Jin, D. (2019). TRAF1 exacerbates myocardial ischemia reperfusion injury via ASK1‐JNK/p38 signaling. Journal of the American Heart Association, 8(21), e012575. https://doi.org/10.1161/JAHA.119.012575.
      Yang, R., Zhang, X., Xing, P., Zhang, S., Zhang, F., Wang, J., Yu, J., Zhu, X., & Chang, P. (2022). Grpel2 alleviates myocardial ischemia/reperfusion injury by inhibiting MCU‐mediated mitochondrial calcium overload. Biochemical and Biophysical Research Communications, 609, 169–175. https://doi.org/10.1016/j.bbrc.2022.04.014.
      You, Z., & Changsheng, M. (2019). Clinical significance of serum cTnI, CK‐MB, and echocardiography detection in the diagnosis of elderly patients with acute myocardial infarction. Chinese Journal of Gerontology, 39(3), 531–533.
      Yu, Q., Cai, R. L., Shao, X. F., Zhang, Y. T., Wei, X. T., & Hu, L. (2021). Effect of electroacupuncture preconditioning on the contents of dopamine and 5‐hydroxytryptamine in lateral hypothalamus area and cerebellar fastigial nucleus of rats with myocardial ischemia‐reperfusion injury. Zhongguo Zhen Jiu, 41(1), 525–530.
      Yuan, J., Wang, J. M., Cai, Y., Fu, S. P., Zhu, B. M., & Lu, S. F. (2019). Effects of electroacupuncture on sympathetic nerve‐related substance in myocardial tissue in mice with myocardial ischemia. Zhongguo Zhen Jiu, 39(5), 501–506. https://doi.org/10.13703/j.0255-2930.2019.05.011.
      Yuan, J., Wang, J. M., Cai, Y., Lu, S. F., & Zhu, B. M. (2019). Correlation between ischemic myocardial injury and inflammatory reaction, and anti‐inflammatory effect of acupuncture. Zhen Ci Yan Jiu, 44(4), 302–306. https://doi.org/10.13702/j.1000-0607.180204.
      Zhang, F., Lin‐bin, W., Ling, H., et al. (2022). Study on the central neural pathway and the relationship between the heart and small intestine via a dual neural tracer. PLoS ONE, 17(11), e0277644. https://doi.org/10.1371/journal.pone.0277644.
      Zhang, T., Yang, W. X., Wang, Y. L., Yuan, J., Qian, Y., Sun, Q. M., Yu, M. L., Fu, S. P., Xu, B., & Lu, S. F. (2020). Electroacupuncture preconditioning attenuates acute myocardial ischemia injury through inhibiting NLRP3 inflammasome activation in mice. Life Sciences, 248, 117451. https://doi.org/10.1016/j.lfs.2020.117451.
      Zhao, L., Li, D., Zheng, H., Chang, X., Cui, J., Wang, R., Shi, J., Fan, H., Li, Y., Sun, X., Zhang, F., Wu, X., & Liang, F. (2019). Acupuncture as adjunctive therapy for chronic stable angina: A randomized clinical trial. JAMA Internal Medicine, 179(10), 1388–1397. https://doi.org/10.1001/jamainternmed.2019.2407.
      Zheng, H., Katsurada, K., Nandi, S., Li, Y., & Patel, K. P. (2022). A critical role for the paraventricular nucleus of the hypothalamus in the regulation of the volume reflex in normal and various cardiovascular disease states. Current Hypertension Reports, 24(7), 235–246. https://doi.org/10.1007/s11906-022-01187-4.
      Zijian, W. (2013). Effects of acupuncture at “Neiguan” “Shenmen” acupoints on paraventricular nucleus and the content of serum 5‐HT in hyerlipidemia rats after myocardial infarction. Acupuncture Research, 38(6), 482–487.
    • Grant Information:
      2023CXMMTCM019 Research Funds of Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM; 82074536 Data Center of Management Science, National Natural Science Foundation of China - Peking University; 82104999 Data Center of Management Science, National Natural Science Foundation of China - Peking University; 2022AH020043 Anhui Province University Scientific Research Project; 2022AH030062 Anhui Province University Scientific Research Project; gxgwfx2019025 Anhui Province University Outstanding Top Talent Cultivation Funding Project; gxgnfx2022014 Anhui Province Excellent Youth Backbone Talent Domestic Visit and Training Program; 2108085QH364 Natural Science Foundation of Anhui Province; 2108085Y30 Natural Science Foundation of Anhui Province
    • Contributed Indexing:
      Keywords: electroacupuncture (EA); hypothalamic paraventricular nucleus; myocardial ischemia–reperfusion injury (MIRI); neural pathway; rostral ventrolateral medulla
    • Accession Number:
      0 (Troponin I)
      0 (Proto-Oncogene Proteins c-fos)
    • Publication Date:
      Date Created: 20240726 Date Completed: 20240903 Latest Revision: 20240903
    • Publication Date:
      20240903
    • Accession Number:
      10.1111/ejn.16480
    • Accession Number:
      39054660