Mechanistic Research and Therapeutic Advances of the JAK/STAT Signaling Pathway in Myocardial Infarction
Journal: Journal of Clinical Medicine Research DOI: 10.32629/jcmr.v6i1.3723
Abstract
Myocardial infarction (MI) is a critical heart disease with high incidence and mortality. Current treatments like coronary reperfusion have limitations, including risks of reperfusion injury and bleeding. Understanding MI's molecular mechanisms is vital for developing new strategies. The JAK/STAT pathway plays a key role in MI by regulating inflammation, apoptosis, fibrosis, oxidative stress, and angiogenesis. This article reviews its role in MI pathophysiology and its therapeutic potential, laying a foundation for innovative treatments. As research progresses, modulating JAK/STAT shows promise in reducing myocardial damage and inflammation, offering hope for future effective therapies.
Keywords
janus kinase (JAK), signal transducer and activator of transcription (STAT), myocardial infarction (MI), therapeutic strategies
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[31] Wang Z, Li J, Xiao W, et al. The STAT3 inhibitor S3I-201 suppresses fibrogenesis and angiogenesis in liver fibrosis [J]. Lab Invest, 2018, 98(12): 1600-1613.
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[35] Kang H-J, Kim H-S. G-CSF- and erythropoietin-based cell therapy: a promising strategy for angiomyogenesis in myocardial infarction [J]. Expert Review of Cardiovascular Therapy, 2008, 6(5): 703-713.
[36] Ai Y, Meng Y, Yan B, et al. The biochemical pathways of apoptotic, necroptotic, pyroptotic, and ferroptotic cell death [J]. Molecular Cell, 2024, 84(1): 170-179.
[37] Barry S P, Townsend P A, Latchman D S, et al. Role of the JAK–STAT pathway in myocardial injury [J]. Trends in Molecular Medicine, 2007, 13(2): 82-89.
[38] Zhu J, Yao K, Guo J, et al. miR-181a and miR-150 regulate dendritic cell immune inflammatory responses and cardiomyocyte apoptosis via targeting JAK1-STAT1/c-Fos pathway [J]. J Cell Mol Med, 2017, 21(11): 2884-2895.
[39] Kim H S, Lee M-S. STAT1 as a key modulator of cell death [J]. Cellular Signalling, 2007, 19(3): 454-465.
[40] Zhang J, Xu Y, Wei C, et al. Macrophage neogenin deficiency exacerbates myocardial remodeling and inflammation after acute myocardial infarction through JAK1-STAT1 signaling [J]. Cellular and Molecular Life Sciences, 2023, 80(11).
[41] Wang W, Chen X K, Zhou L, et al. Chemokine CCL2 promotes cardiac regeneration and repair in myocardial infarction mice via activation of the JNK/STAT3 axis [J]. Acta Pharmacol Sin, 2024, 45(4): 728-737.
[42] Dong W, Chen J, Wang Y, et al. miR-206 alleviates LPS-induced inflammatory injury in cardiomyocytes via directly targeting USP33 to inhibit the JAK2/STAT3 signaling pathway [J]. Mol Cell Biochem, 2024, 479(4): 929-940.
[43] Kleinbongard P. Perspective: mitochondrial STAT3 in cardioprotection [J]. Basic Res Cardiol, 2023, 118(1): 32.
[44] Wei G, Li C, Jia X, et al. Extracellular vesicle-derived CircWhsc1 promotes cardiomyocyte proliferation and heart repair by activating TRIM59/STAT3/Cyclin B2 pathway [J]. J Adv Res, 2023, 53: 199-218.
[45] Nakao S, Tsukamoto T, Ueyama T, et al. STAT3 for Cardiac Regenerative Medicine: Involvement in Stem Cell Biology, Pathophysiology, and Bioengineering [J]. Int J Mol Sci, 2020, 21(6).
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[49] Butler J, Jones W S, Udell J A, et al. Empagliflozin after Acute Myocardial Infarction [J]. New England Journal of Medicine, 2024, 390(16): 1455-1466.
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[2] Bergmark B A, Mathenge N, Merlini P A, et al. Acute coronary syndromes [J]. Lancet, 2022, 399(10332): 1347-1358.
[3] Doenst T, Haverich A, Serruys P, et al. PCI and CABG for Treating Stable Coronary Artery Disease: JACC Review Topic of the Week [J]. J Am Coll Cardiol, 2019, 73(8): 964-976.
[4] Philips R L, Wang Y, Cheon H, et al. The JAK-STAT pathway at 30: Much learned, much more to do [J]. Cell, 2022, 185(21): 3857-3876.
[5] Raychaudhuri S, Cheema K S, Raychaudhuri S K, et al. Janus kinase–signal transducers and activators of transcription cell signaling in Spondyloarthritis: rationale and evidence for JAK inhibition [J]. Current Opinion in Rheumatology, 2021, 33(4): 348-355.
[6] Banerjee S, Biehl A, Gadina M, et al. JAK–STAT Signaling as a Target for Inflammatory and Autoimmune Diseases: Current and Future Prospects [J]. Drugs, 2017, 77(5): 521-546.
[7] Liu J, Wang F, Luo F. The Role of JAK/STAT Pathway in Fibrotic Diseases: Molecular and Cellular Mechanisms [J]. Biomolecules, 2023, 13(1): 119.
[8] Liu Y, Wang W, Zhang J, et al. JAK/STAT signaling in diabetic kidney disease [J]. Frontiers in Cell and Developmental Biology, 2023, 11.
[9] Swiatek-Machado K, Kaminska B. STAT Signaling in Glioma Cells [Z]. Advances in Experimental Medicine and Biology. Springer International Publishing. 2020: 203-222.10.1007/978-3-030-30651-9_10
[10] Yu H, Jove R. The STATs of cancer — new molecular targets come of age [J]. Nature Reviews Cancer, 2004, 4(2): 97-105.
[11] Hu X, li J, Fu M, et al. The JAK/STAT signaling pathway: from bench to clinic [J]. Signal Transduction and Targeted Therapy, 2021, 6(1).
[12] Bejerano T, Etzion S, Elyagon S, et al. Nanoparticle Delivery of miRNA-21 Mimic to Cardiac Macrophages Improves Myocardial Remodeling after Myocardial Infarction [J]. Nano Letters, 2018, 18(9): 5885-5891.
[13] Hu Q, Bian Q, Rong D, et al. JAK/STAT pathway: Extracellular signals, diseases, immunity, and therapeutic regimens [J]. Frontiers in Bioengineering and Biotechnology, 2023, 11.
[14] Xia T, Zhang M, Lei W, et al. Advances in the role of STAT3 in macrophage polarization [J]. Frontiers in Immunology, 2023, 14.
[15] Li J, Shen D, Tang J, et al. IL33 attenuates ventricular remodeling after myocardial infarction through inducing alternatively activated macrophages ethical standards statement [J]. European Journal of Pharmacology, 2019, 854: 307-319.
[16] Wang N, Liu C, Wang X, et al. Hyaluronic Acid Oligosaccharides Improve Myocardial Function Reconstruction and Angiogenesis against Myocardial Infarction by Regulation of Macrophages [J]. Theranostics, 2019, 9(7): 1980-1992.
[17] Huang C-K, Chen Z, Zhou Z, et al. RNF149 Destabilizes IFNGR1 in Macrophages to Favor Post-Infarction Cardiac Repair [J]. Circulation Research, 2024.
[18] Niu X-H, Liu R-H, Lv X, et al. Activating α7nAChR helps post-myocardial infarction healing by regulating macrophage polarization via the STAT3 signaling pathway [J]. Inflammation Research, 2023, 72(4): 879-892.
[19] Wang J, Liu M, Wu Q, et al. Human Embryonic Stem Cell-Derived Cardiovascular Progenitors Repair Infarcted Hearts Through Modulation of Macrophages via Activation of Signal Transducer and Activator of Transcription 6 [J]. Antioxidants & Redox Signaling, 2019, 31(5): 369-386.
[20] Fan D, Takawale A, Lee J, et al. Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease [J]. Fibrogenesis & Tissue Repair, 2012, 5(1).
[21] Pang Q, You L, Meng X, et al. Regulation of the JAK/STAT signaling pathway: The promising targets for cardiovascular disease [J]. Biochemical Pharmacology, 2023, 213: 115587.
[22] Liu J, Wang F, Luo F. The Role of JAK/STAT Pathway in Fibrotic Diseases: Molecular and Cellular Mechanisms [J/OL] 2023, 13(1):119
[23] Jiang H, Yang J, Li T, et al. JAK/STAT3 signaling in cardiac fibrosis: a promising therapeutic target [J]. Frontiers in Pharmacology, 2024, 15.
[24] Zhang Q, Wang L, Wang S, et al. Signaling pathways and targeted therapy for myocardial infarction [J]. Signal Transduction and Targeted Therapy, 2022, 7(1).
[25] Wang Y, Wang M, Samuel C S, et al. Preclinical rodent models of cardiac fibrosis [J]. British Journal of Pharmacology, 2021, 179(5): 882-899.
[26] Niu W, Zhu M, Wang M, et al. Discovery and development of benzene sulfonamide derivatives as anti-hepatic fibrosis agents [J]. Bioorg Med Chem Lett, 2023, 88: 129290.
[27] Di Martino J S, Nobre A R, Mondal C, et al. A tumor-derived type III collagen-rich ECM niche regulates tumor cell dormancy [J]. Nat Cancer, 2022, 3(1): 90-107.
[28] Ye L, Huang J, Liang X, et al. Jiawei Taohe Chengqi Decoction attenuates CCl(4) induced hepatic fibrosis by inhibiting HSCs activation via TGF-β1/CUGBP1 and IFN-γ/Smad7 pathway [J]. Phytomedicine, 2024, 133: 155916.
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[30] Bao H, Wang X, Zhou H, et al. PCSK9 regulates myofibroblast transformation through the JAK2/STAT3 pathway to regulate fibrosis after myocardial infarction [J]. Biochem Pharmacol, 2024, 220: 115996.
[31] Wang Z, Li J, Xiao W, et al. The STAT3 inhibitor S3I-201 suppresses fibrogenesis and angiogenesis in liver fibrosis [J]. Lab Invest, 2018, 98(12): 1600-1613.
[32] Xia B, Ding J, Li Q, et al. Loganin protects against myocardial ischemia-reperfusion injury by modulating oxidative stress and cellular apoptosis via activation of JAK2/STAT3 signaling [J]. International Journal of Cardiology, 2024, 395: 131426.
[33] Rao T, Tong H, Li J, et al. Exploring the role and mechanism of hyperoside against cardiomyocyte injury in mice with myocardial infarction based on JAK2/STAT3 signaling pathway [J]. Phytomedicine, 2024, 128: 155319.
[34] Hilfiker-Kleiner D, Hilfiker A, Fuchs M, et al. Signal Transducer and Activator of Transcription 3 Is Required for Myocardial Capillary Growth, Control of Interstitial Matrix Deposition, and Heart Protection From Ischemic Injury [J]. Circulation Research, 2004, 95(2): 187-195.
[35] Kang H-J, Kim H-S. G-CSF- and erythropoietin-based cell therapy: a promising strategy for angiomyogenesis in myocardial infarction [J]. Expert Review of Cardiovascular Therapy, 2008, 6(5): 703-713.
[36] Ai Y, Meng Y, Yan B, et al. The biochemical pathways of apoptotic, necroptotic, pyroptotic, and ferroptotic cell death [J]. Molecular Cell, 2024, 84(1): 170-179.
[37] Barry S P, Townsend P A, Latchman D S, et al. Role of the JAK–STAT pathway in myocardial injury [J]. Trends in Molecular Medicine, 2007, 13(2): 82-89.
[38] Zhu J, Yao K, Guo J, et al. miR-181a and miR-150 regulate dendritic cell immune inflammatory responses and cardiomyocyte apoptosis via targeting JAK1-STAT1/c-Fos pathway [J]. J Cell Mol Med, 2017, 21(11): 2884-2895.
[39] Kim H S, Lee M-S. STAT1 as a key modulator of cell death [J]. Cellular Signalling, 2007, 19(3): 454-465.
[40] Zhang J, Xu Y, Wei C, et al. Macrophage neogenin deficiency exacerbates myocardial remodeling and inflammation after acute myocardial infarction through JAK1-STAT1 signaling [J]. Cellular and Molecular Life Sciences, 2023, 80(11).
[41] Wang W, Chen X K, Zhou L, et al. Chemokine CCL2 promotes cardiac regeneration and repair in myocardial infarction mice via activation of the JNK/STAT3 axis [J]. Acta Pharmacol Sin, 2024, 45(4): 728-737.
[42] Dong W, Chen J, Wang Y, et al. miR-206 alleviates LPS-induced inflammatory injury in cardiomyocytes via directly targeting USP33 to inhibit the JAK2/STAT3 signaling pathway [J]. Mol Cell Biochem, 2024, 479(4): 929-940.
[43] Kleinbongard P. Perspective: mitochondrial STAT3 in cardioprotection [J]. Basic Res Cardiol, 2023, 118(1): 32.
[44] Wei G, Li C, Jia X, et al. Extracellular vesicle-derived CircWhsc1 promotes cardiomyocyte proliferation and heart repair by activating TRIM59/STAT3/Cyclin B2 pathway [J]. J Adv Res, 2023, 53: 199-218.
[45] Nakao S, Tsukamoto T, Ueyama T, et al. STAT3 for Cardiac Regenerative Medicine: Involvement in Stem Cell Biology, Pathophysiology, and Bioengineering [J]. Int J Mol Sci, 2020, 21(6).
[46] Uciechowski P, Dempke W C M. Interleukin-6: A Masterplayer in the Cytokine Network [J]. Oncology, 2020, 98(3): 131-137.
[47] Schulte D M, Waetzig G H, Schuett H, et al. Case Report: Arterial Wall Inflammation in Atherosclerotic Cardiovascular Disease is Reduced by Olamkicept (sgp130Fc) [J]. Frontiers in Pharmacology, 2022, 13.
[48] Virtanen A, Spinelli F R, Telliez J B, et al. JAK inhibitor selectivity: new opportunities, better drugs? [J]. Nat Rev Rheumatol, 2024, 20(10): 649-665.
[49] Butler J, Jones W S, Udell J A, et al. Empagliflozin after Acute Myocardial Infarction [J]. New England Journal of Medicine, 2024, 390(16): 1455-1466.
[50] Hernandez A F, Udell J A, Jones W S, et al. Effect of Empagliflozin on Heart Failure Outcomes After Acute Myocardial Infarction: Insights From the EMPACT-MI Trial [J]. Circulation, 2024, 149(21): 1627-1638.
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