川崎病与氧化应激的研究进展
Research Progress of Kawasaki Disease and Oxidative Stress
摘要: 氧化应激是川崎病发病机制之一,活性氧的过量产生将导致氧化应激,控制活性氧的产生将有助于减轻氧化应激的程度,有可能改善川崎病患儿预后,因此抗氧化剂可以作为川崎病急性期的辅助疗法,特别是针对特定细胞器的靶向抗氧化剂有望成为川崎病的新型治疗措施。本文将对活性氧的产生和在川崎病中产生的病理作用,以及抗氧化剂目前的研究进展进行讨论。
Abstract: Oxidative stress is one of the pathogenesis of Kawasaki disease. Excessive production of reactive oxygen species will lead to oxidative stress. Controlling the production of reactive oxygen species will help to reduce the degree of oxidative stress and may improve the prognosis of children with Kawasaki disease. Therefore, antioxidants can be used as an adjuvant therapy for the acute phase of Kawasaki disease, especially for specific organelles. Targeted antioxidants are expected to become a new treatment for Kawasaki disease. This article will discuss the production of reactive oxygen species and the pathological effects in Kawasaki disease, as well as the current research progress of antioxidants.
文章引用:蒋颖, 刘丰贤, 陈春余, 张维涛, 何健峰. 川崎病与氧化应激的研究进展[J]. 临床医学进展, 2024, 14(8): 1244-1254. https://doi.org/10.12677/acm.2024.1482346

参考文献

[1] Valko, M., Rhodes, C.J., Moncol, J., Izakovic, M. and Mazur, M. (2006) Free Radicals, Metals and Antioxidants in Oxidative Stress-Induced Cancer. Chemico-Biological Interactions, 160, 1-40. [Google Scholar] [CrossRef] [PubMed]
[2] Valko, M., Leibfritz, D., Moncol, J., Cronin, M.T.D., Mazur, M. and Telser, J. (2007) Free Radicals and Antioxidants in Normal Physiological Functions and Human Disease. The International Journal of Biochemistry & Cell Biology, 39, 44-84. [Google Scholar] [CrossRef] [PubMed]
[3] Straface, E., Marchesi, A., Gambardella, L., Metere, A., Tarissi de Jacobis, I., Viora, M., et al. (2012) Does Oxidative Stress Play a Critical Role in Cardiovascular Complications of Kawasaki Disease? Antioxidants & Redox Signaling, 17, 1441-1446. [Google Scholar] [CrossRef] [PubMed]
[4] Yoshimura, K., Tatsumi, K., Iharada, A., Tsuji, S., Tateiwa, A., Teraguchi, M., et al. (2008) Increased Nitric Oxide Production by Neutrophils in Early Stage of Kawasaki Disease. European Journal of Pediatrics, 168, 1037-1041. [Google Scholar] [CrossRef] [PubMed]
[5] Cai, H. and Harrison, D.G. (2000) Endothelial Dysfunction in Cardiovascular Diseases: The Role of Oxidant Stress. Circulation Research, 87, 840-844. [Google Scholar] [CrossRef] [PubMed]
[6] Rauf, A., Khalil, A.A., Awadallah, S., Khan, S.A., Abu‐Izneid, T., Kamran, M., et al. (2023) Reactive Oxygen Species in Biological Systems: Pathways, Associated Diseases, and Potential Inhibitors—A Review. Food Science & Nutrition, 12, 675-693. [Google Scholar] [CrossRef] [PubMed]
[7] Cadenas, E. (1989) Biochemistry Of Oxygen Toxicity. Annual Review of Biochemistry, 58, 79-110. [Google Scholar] [CrossRef] [PubMed]
[8] Kukreja, R.C. and Hess, M.L. (1992) The Oxygen Free Radical System: From Equations through Membrane-Protein Interactions to Cardiovascular Injury and Protection. Cardiovascular Research, 26, 641-655. [Google Scholar] [CrossRef] [PubMed]
[9] Halliwell, B. and Gutteridge, J.M.C. (2015). Free Radicals in Biology and Medicine. Oxford University Press.[CrossRef
[10] Forrester, S.J., Kikuchi, D.S., Hernandes, M.S., Xu, Q. and Griendling, K.K. (2018) Reactive Oxygen Species in Metabolic and Inflammatory Signaling. Circulation Research, 122, 877-902. [Google Scholar] [CrossRef] [PubMed]
[11] Tejero, J., Shiva, S. and Gladwin, M.T. (2019) Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation. Physiological Reviews, 99, 311-379. [Google Scholar] [CrossRef] [PubMed]
[12] Förstermann, U., Closs, E.I., Pollock, J.S., Nakane, M., Schwarz, P., Gath, I., et al. (1994) Nitric Oxide Synthase Isozymes. Characterization, Purification, Molecular Cloning, and Functions. Hypertension, 23, 1121-1131. [Google Scholar] [CrossRef] [PubMed]
[13] Infante, T., Costa, D. and Napoli, C. (2021) Novel Insights Regarding Nitric Oxide and Cardiovascular Diseases. Angiology, 72, 411-425. [Google Scholar] [CrossRef] [PubMed]
[14] Pautz, A., Art, J., Hahn, S., Nowag, S., Voss, C. and Kleinert, H. (2010) Regulation of the Expression of Inducible Nitric Oxide Synthase. Nitric Oxide, 23, 75-93. [Google Scholar] [CrossRef] [PubMed]
[15] Xia, Y. and Zweier, J.L. (1997) Superoxide and Peroxynitrite Generation from Inducible Nitric Oxide Synthase in Macrophages. Proceedings of the National Academy of Sciences of the United States of America, 94, 6954-6958. [Google Scholar] [CrossRef] [PubMed]
[16] Buttery, L.D., Springall, D.R., Chester, A.H., et al. (1996) Inducible Nitric Oxide Synthase Is Present within Human Atherosclerotic Lesions and Promotes the Formation and Activity of Peroxynitrite. Laboratory Investigation, 75, 77-85.
[17] Förstermann, U. and Münzel, T. (2006) Endothelial Nitric Oxide Synthase in Vascular Disease: From Marvel to Menace. Circulation, 113, 1708-1714. [Google Scholar] [CrossRef] [PubMed]
[18] Chen, K., Lin, W. and Kuo, H. (2021) Chemical and Biochemical Aspects of Molecular Hydrogen in Treating Kawasaki Disease and Covid-19. Chemical Research in Toxicology, 34, 952-958. [Google Scholar] [CrossRef] [PubMed]
[19] Iizuka, T., Oishi, K., Sasaki, M., Hatanaka, Y., Minatogawa, Y., Uemura, S., et al. (1997) Nitric Oxide and Aneurysm Formation in Kawasaki Disease. Acta Paediatrica, 86, 470-473. [Google Scholar] [CrossRef] [PubMed]
[20] Li, Q., Wang, Y., Chen, K., Zhou, Q., Wei, W., Wang, Y., et al. (2010) The Role of Oxidized Low-Density Lipoprotein in Breaking Peripheral Th17/Treg Balance in Patients with Acute Coronary Syndrome. Biochemical and Biophysical Research Communications, 394, 836-842. [Google Scholar] [CrossRef] [PubMed]
[21] Yahata, T., Suzuki, C., Hamaoka, A., Fujii, M. and Hamaoka, K. (2011) Dynamics of Reactive Oxygen Metabolites and Biological Antioxidant Potential in the Acute Stage of Kawasaki Disease. Circulation Journal, 75, 2453-2459. [Google Scholar] [CrossRef] [PubMed]
[22] Shen, C.T. and Wang, N.K. (2001) Antioxidants May Mitigate the Deterioration of Coronary Arteritis in Patients with Kawasaki Disease Unresponsive to High-Dose Intravenous γ-Globulin. Pediatric Cardiology, 22, 419-422. [Google Scholar] [CrossRef] [PubMed]
[23] 解玉. 川崎病冠状动脉病变与内皮功能障碍 [J]. 中国当代儿科杂志, 2003(2): 177-9+83.
[24] Steven, S., Frenis, K., Oelze, M., Kalinovic, S., Kuntic, M., Bayo Jimenez, M.T., et al. (2019) Vascular Inflammation and Oxidative Stress: Major Triggers for Cardiovascular Disease. Oxidative Medicine and Cellular Longevity, 2019, Article ID: 7092151. [Google Scholar] [CrossRef] [PubMed]
[25] Takahashi, K., Oharaseki, T., Naoe, S., Wakayama, M. and Yokouchi, Y. (2005) Neutrophilic Involvement in the Damage to Coronary Arteries in Acute Stage of Kawasaki Disease. Pediatrics International, 47, 305-310. [Google Scholar] [CrossRef] [PubMed]
[26] Seki, M. and Minami, T. (2022) Kawasaki Disease: Pathology, Risks, and Management. Vascular Health and Risk Management, 18, 407-416. [Google Scholar] [CrossRef] [PubMed]
[27] Iemura, M. (2000) Long Term Consequences of Regressed Coronary Aneurysms after Kawasaki Disease: Vascular Wall Morphology and Function. Heart, 83, 307-311. [Google Scholar] [CrossRef] [PubMed]
[28] Ingold, K.U., Bowry, V.W., Stocker, R. and Walling, C. (1993) Autoxidation of Lipids and Antioxidation by Alpha-Tocopherol and Ubiquinol in Homogeneous Solution and in Aqueous Dispersions of Lipids: Unrecognized Consequences of Lipid Particle Size as Exemplified by Oxidation of Human Low Density Lipoprotein. Proceedings of the National Academy of Sciences of the United States of America, 90, 45-49. [Google Scholar] [CrossRef] [PubMed]
[29] Gęgotek, A. and Skrzydlewska, E. (2023) Ascorbic Acid as Antioxidant. Vitamins and Hormones, 121, 247-270. [Google Scholar] [CrossRef] [PubMed]
[30] Frei, B. (1994) Reactive Oxygen Species and Antioxidant Vitamins: Mechanisms of Action. The American Journal of Medicine, 97, S5-S13. [Google Scholar] [CrossRef] [PubMed]
[31] Retsky, K.L., Freeman, M.W. and Frei, B. (1993) Ascorbic Acid Oxidation Product(s) Protect Human Low Density Lipoprotein against Atherogenic Modification. Anti-Rather than Prooxidant Activity of Vitamin C in the Presence of Transition Metal Ions. Journal of Biological Chemistry, 268, 1304-1309. [Google Scholar] [CrossRef] [PubMed]
[32] Philip, S., Lee, W., Cherian, K.M., Wu, M. and Lue, H. (2017) Role of Antioxidants in Horse Serum-Mediated Vasculitis in Swine: Potential Relevance to Early Treatment in Mitigation of Coronary Arteritis in Kawasaki Disease. Pediatrics & Neonatology, 58, 328-337. [Google Scholar] [CrossRef] [PubMed]
[33] Deng, Y., Xiang, H., Chang, Q. and Li, C. (2002) Evaluation by High-Resolution Ultrasonography of Endothelial Function in Brachial Artery after Kawasaki Disease and the Effects of Intravenous Administration of Vitamin C. Circulation Journal, 66, 908-912. [Google Scholar] [CrossRef] [PubMed]
[34] Sabri, M.R., Tavana, E.N., Ahmadi, A., et al. (2015) Does Vitamin C Improve Endothelial Function in Patients with Kawa-Saki Disease? Journal of Research in Medical Sciences, 20, 32-36.
[35] Bilheimer, D.W., Grundy, S.M., Brown, M.S. and Goldstein, J.L. (1983) Mevinolin and Colestipol Stimulate Receptor-Mediated Clearance of Low Density Lipoprotein from Plasma in Familial Hypercholesterolemia Heterozygotes. Proceedings of the National Academy of Sciences of the United States of America, 80, 4124-4128. [Google Scholar] [CrossRef] [PubMed]
[36] Lv, S., Liu, Y., Zou, Z., et al. (2015) The Impact of Statins Therapy on Disease Activity and Inflammatory Factor in Patients with Rheumatoid Arthritis: A Meta-Analysis. Clinical and Experimental Rheumatology, 33, 69-76.
[37] Inanc, M.T., Kalay, N., Heyit, T., Ozdogru, I., Kaya, M.G., Dogan, A., et al. (2010) Effects of Atorvastatin and Lisinopril on Endothelial Dysfunction in Patients with Behçet’s Disease. Echocardiography, 27, 997-1003. [Google Scholar] [CrossRef] [PubMed]
[38] Ray, J.G., Mamdani, M., Tsuyuki, R.T., Anderson, D.R., Yeo, E.L. and Laupacis, A. (2001) Use of Statins and the Subsequent Development of Deep Vein Thrombosis. Archives of Internal Medicine, 161, 1405-1410. [Google Scholar] [CrossRef] [PubMed]
[39] Delbosc, S., Morena, M., Djouad, F., Ledoucen, C., Descomps, B. and Cristol, J. (2002) Statins, 3-Hydroxy-3-Methylglutaryl Coenzyme a Reductase Inhibitors, Are Able to Reduce Superoxide Anion Production by NADPH Oxidase in Thp-1-Derived Monocytes. Journal of Cardiovascular Pharmacology, 40, 611-617. [Google Scholar] [CrossRef] [PubMed]
[40] Hoffman, R., Brook, G.J. and Aviram, M. (1992) Hypolipidemic Drugs Reduce Lipoprotein Susceptibility to Undergo Lipid Peroxidation: In Vitro and Ex Vivo Studies. Atherosclerosis, 93, 105-113. [Google Scholar] [CrossRef] [PubMed]
[41] Kosmidou, I., Moore, J.P., Weber, M. and Searles, C.D. (2007) Statin Treatment and 3’ Polyadenylation of eNOS mRNA. Arteriosclerosis, Thrombosis, and Vascular Biology, 27, 2642-2649. [Google Scholar] [CrossRef] [PubMed]
[42] Balakumar, P., Kathuria, S., Taneja, G., Kalra, S. and Mahadevan, N. (2012) Is Targeting eNOS a Key Mechanistic Insight of Cardiovascular Defensive Potentials of Statins? Journal of Molecular and Cellular Cardiology, 52, 83-92. [Google Scholar] [CrossRef] [PubMed]
[43] Motoji, Y., Fukazawa, R., Matsui, R., Abe, Y., Uehara, I., Watanabe, M., et al. (2022) Statins Show Anti-Atherosclerotic Effects by Improving Endothelial Cell Function in a Kawasaki Disease-Like Vasculitis Mouse Model. International Journal of Molecular Sciences, 23, Article 16108. [Google Scholar] [CrossRef] [PubMed]
[44] Lim, S. and Barter, P. (2014) Antioxidant Effects of Statins in the Management of Cardiometabolic Disorders. Journal of Atherosclerosis and Thrombosis, 21, 997-1010. [Google Scholar] [CrossRef] [PubMed]
[45] Franco, A., Shimizu, C., Tremoulet, A.H. and Burns, J.C. (2010) Memory T-Cells and Characterization of Peripheral T-Cell Clones in Acute Kawasaki Disease. Autoimmunity, 43, 317-324. [Google Scholar] [CrossRef] [PubMed]
[46] Duan, C., Du, Z., Wang, Y. and Jia, L. (2014) Effect of Pravastatin on Endothelial Dysfunction in Children with Medium to Giant Coronary Aneurysms Due to Kawasaki Disease. World Journal of Pediatrics, 10, 232-237. [Google Scholar] [CrossRef] [PubMed]
[47] Hamaoka, A., Hamaoka, K., Yahata, T., Fujii, M., Ozawa, S., Toiyama, K., et al. (2010) Effects of HMG-CoA Reductase Inhibitors on Continuous Post-Inflammatory Vascular Remodeling Late after Kawasaki Disease. Journal of Cardiology, 56, 245-253. [Google Scholar] [CrossRef] [PubMed]
[48] Canas, J.A., Ross, J.L., Taboada, M.V., Sikes, K.M., Damaso, L.C., Hossain, J., et al. (2014) A Randomized, Double Blind, Placebo-Controlled Pilot Trial of the Safety and Efficacy of Atorvastatin in Children with Elevated Low-Density Lipoprotein Cholesterol (LDL-C) and Type 1 Diabetes. Pediatric Diabetes, 16, 79-89. [Google Scholar] [CrossRef] [PubMed]
[49] Tremoulet, A.H., Jain, S., Jone, P., Best, B.M., Duxbury, E.H., Franco, A., et al. (2019) Phase I/IIa Trial of Atorvastatin in Patients with Acute Kawasaki Disease with Coronary Artery Aneurysm. The Journal of Pediatrics, 215, 107-117.E12. [Google Scholar] [CrossRef] [PubMed]
[50] Simsek, B., Selte, A., Egeli, B.H. and Çakatay, U. (2021) Effects of Vitamin Supplements on Clinical Cardiovascular Outcomes: Time to Move On!—A Comprehensive Review. Clinical Nutrition ESPEN, 42, 1-14. [Google Scholar] [CrossRef] [PubMed]
[51] Gutteridge, J.M.C. and Halliwell, B. (2010) Antioxidants: Molecules, Medicines, and Myths. Biochemical and Biophysical Research Communications, 393, 561-564. [Google Scholar] [CrossRef] [PubMed]
[52] Vivekananthan, D.P., Penn, M.S., Sapp, S.K., Hsu, A. and Topol, E.J. (2003) Use of Antioxidant Vitamins for the Prevention of Cardiovascular Disease: Meta-Analysis of Randomised Trials. The Lancet, 361, 2017-2023. [Google Scholar] [CrossRef] [PubMed]
[53] Cochemé, H.M. and Murphy, M.P. (2010) Can Antioxidants Be Effective Therapeutics? Current Opinion in Investigational Drugs, 11, 426-431.
[54] Ross, M.F., Kelso, G.F., Blaikie, F.H., James, A.M., Cochemé, H.M., Filipovska, A., et al. (2005) Lipophilic Triphenylphosphonium Cations as Tools in Mitochondrial Bioenergetics and Free Radical Biology. Biochemistry (Moscow), 70, 222-230. [Google Scholar] [CrossRef] [PubMed]
[55] Smith, R.A.J., Porteous, C.M., Coulter, C.V. and Murphy, M.P. (1999) Selective Targeting of an Antioxidant to Mitochondria. European Journal of Biochemistry, 263, 709-716. [Google Scholar] [CrossRef] [PubMed]
[56] Kelso, G.F., Porteous, C.M., Coulter, C.V., Hughes, G., Porteous, W.K., Ledgerwood, E.C., et al. (2001) Selective Targeting of a Redox-Active Ubiquinone to Mitochondria within Cells: Antioxidant and Antiapoptotic Properties. Journal of Biological Chemistry, 276, 4588-4596. [Google Scholar] [CrossRef] [PubMed]
[57] Filipovska, A., Kelso, G.F., Brown, S.E., Beer, S.M., Smith, R.A.J. and Murphy, M.P. (2005) Synthesis and Characterization of a Triphenylphosphonium-Conjugated Peroxidase Mimetic. Insights into the Interaction of Ebselen with Mitochondria. Journal of Biological Chemistry, 280, 24113-24126. [Google Scholar] [CrossRef] [PubMed]
[58] Smith, R.A.J., Hartley, R.C. and Murphy, M.P. (2011) Mitochondria-Targeted Small Molecule Therapeutics and Probes. Antioxidants & Redox Signaling, 15, 3021-3038. [Google Scholar] [CrossRef] [PubMed]
[59] Rodriguez-Cuenca, S., Cochemé, H.M., Logan, A., Abakumova, I., Prime, T.A., Rose, C., et al. (2010) Consequences of Long-Term Oral Administration of the Mitochondria-Targeted Antioxidant MitoQ to Wild-Type Mice. Free Radical Biology and Medicine, 48, 161-172. [Google Scholar] [CrossRef] [PubMed]
[60] Snow, B.J., Rolfe, F.L., Lockhart, M.M., Frampton, C.M., O’Sullivan, J.D., Fung, V., et al. (2010) A Double‐blind, Placebo‐controlled Study to Assess the Mitochondria‐Targeted Antioxidant MitoQ as a Disease‐Modifying Therapy in Parkinson’s Disease. Movement Disorders, 25, 1670-1674. [Google Scholar] [CrossRef] [PubMed]
[61] Gane, E.J., Weilert, F., Orr, D.W., Keogh, G.F., Gibson, M., Lockhart, M.M., et al. (2010) The Mitochondria-Targeted Anti-Oxidant Mitoquinone Decreases Liver Damage in a Phase II Study of Hepatitis C Patients. Liver International, 30, 1019-1026. [Google Scholar] [CrossRef] [PubMed]
[62] Horton, K.L., Stewart, K.M., Fonseca, S.B., Guo, Q. and Kelley, S.O. (2008) Mitochondria-Penetrating Peptides. Chemistry & Biology, 15, 375-382. [Google Scholar] [CrossRef] [PubMed]
[63] Zhao, K., Zhao, G., Wu, D., Soong, Y., Birk, A.V., Schiller, P.W., et al. (2004) Cell-Permeable Peptide Antioxidants Targeted to Inner Mitochondrial Membrane Inhibit Mitochondrial Swelling, Oxidative Cell Death, and Reperfusion Injury. Journal of Biological Chemistry, 279, 34682-34690. [Google Scholar] [CrossRef] [PubMed]
[64] Ren, M., Phoon, C.K.L. and Schlame, M. (2014) Metabolism and Function of Mitochondrial Cardiolipin. Progress in Lipid Research, 55, 1-16. [Google Scholar] [CrossRef] [PubMed]
[65] Liu, S., Soong, Y., Seshan, S.V. and Szeto, H.H. (2014) Novel Cardiolipin Therapeutic Protects Endothelial Mitochondria during Renal Ischemia and Mitigates Microvascular Rarefaction, Inflammation, and Fibrosis. American Journal of Physiology-Renal Physiology, 306, F970-F980. [Google Scholar] [CrossRef] [PubMed]
[66] Yousif, L.F., Stewart, K.M., Horton, K.L. and Kelley, S.O. (2009) Mitochondria‐penetrating Peptides: Sequence Effects and Model Cargo Transport. ChemBioChem, 10, 2081-2088. [Google Scholar] [CrossRef] [PubMed]
[67] Vestweber, D. and Schatz, G. (1988) Mitochondria Can Import Artificial Precursor Proteins Containing a Branched Polypeptide Chain or a Carboxy-Terminal Stilbene Disulfonate. The Journal of cell biology, 107, 2045-2049. [Google Scholar] [CrossRef] [PubMed]
[68] McLachlan, J., Beattie, E., Murphy, M.P., Koh-Tan, C.H.H., Olson, E., Beattie, W., et al. (2014) Combined Therapeutic Benefit of Mitochondria-Targeted Antioxidant, Mitoq10, and Angiotensin Receptor Blocker, Losartan, on Cardiovascular Function. Journal of Hypertension, 32, 555-564. [Google Scholar] [CrossRef] [PubMed]
[69] Hao, S., Ji, J., Zhao, H., Shang, L., Wu, J., Li, H., et al. (2015) Mitochondrion-Targeted Peptide SS-31 Inhibited Oxidized Low-Density Lipoproteins-Induced Foam Cell Formation through Both ROS Scavenging and Inhibition of Cholesterol Influx in RAW264.7 Cells. Molecules, 20, 21287-21297. [Google Scholar] [CrossRef] [PubMed]
[70] Dai, D., Hsieh, E.J., Chen, T., Menendez, L.G., Basisty, N.B., Tsai, L., et al. (2013) Global Proteomics and Pathway Analysis of Pressure-Overload-Induced Heart Failure and Its Attenuation by Mitochondrial-Targeted Peptides. Circulation: Heart Failure, 6, 1067-1076. [Google Scholar] [CrossRef] [PubMed]
[71] Huang, P., Wei, S., Huang, W., Wu, P., Chen, S., Tao, A., et al. (2022) Corrigendum to “Hydrogen Gas Inhalation Enhances Alveolar Macrophage Phagocytosis in an Ovalbumin-Induced Asthma Model” [int. Immunopharmacol. 74 (2019) 105646]. International Immunopharmacology, 112, Article ID: 109124. [Google Scholar] [CrossRef] [PubMed]
[72] Hayashida, K., Sano, M., Ohsawa, I., Shinmura, K., Tamaki, K., Kimura, K., et al. (2008) Inhalation of Hydrogen Gas Reduces Infarct Size in the Rat Model of Myocardial Ischemia-Reperfusion Injury. Biochemical and Biophysical Research Communications, 373, 30-35. [Google Scholar] [CrossRef] [PubMed]
[73] Zeng, Y., Guan, W., Wang, K., Jie, Z., Zou, X., Tan, X., et al. (2023) Effect of Hydrogen/oxygen Therapy for Ordinary COVID-19 Patients: A Propensity-Score Matched Case-Control Study. BMC Infectious Diseases, 23, Article No. 440. [Google Scholar] [CrossRef] [PubMed]
[74] Katsumata, Y., Sano, F., Abe, T., Tamura, T., Fujisawa, T., Shiraishi, Y., et al. (2017) The Effects of Hydrogen Gas Inhalation on Adverse Left Ventricular Remodeling after Percutaneous Coronary Intervention for St-Elevated Myocardial Infarction—First Pilot Study in Humans. Circulation Journal, 81, 940-947. [Google Scholar] [CrossRef] [PubMed]