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Role of mitogen activated protein kinase activated protein kinase 2 in cardiovascular system
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Affiliation:

1.Department of Cardiology, the First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China;2.Key Laboratory of Metabolism on Lipid and Glucose, Center for Lipid Research, Chongqing Medical University, Chongqing 400016, China)

Clc Number:

R54

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    Abstract:

    The development of cardiovascular disease is related to chronic inflammation. p38 mitogen activated protein kinase (p38MAPK) mediated signaling pathway plays an important role in cardiovascular cell inflammation, proliferation, differentiation, migration and metabolism. Inhibition of p38MAPK can effectively inhibit the expression of inflammatory mediators. In terms of safety, p38 inhibitors are unacceptable and it is necessary to study the downstream substrate. Mitogen-actitated protein kinase actitaved protein kinase 2 (MK2) is an important downstream substrate of p38MAPK and is involved in the development of cardiovascular diseases. Therefore, inhibition of MK2 activity is of great clinical significance in the treatment and prevention of cardiovascular diseases. This article mainly reviews the structure and function of MK2 and its role in cardiovascular diseases.

    Reference
    [1] Yokota T, Wang Y.p38 MAP kinases in heart.Gene, 6,5(2):369-376.
    [2] Feng Q, Jing D, Gang W, et al.Pivotal role of mitogen-activated protein kinase-activated protein kinase 2 in inflammatory pulmonary diseases.Curr Protein Pept Sci, 6,7(4):332-342.
    [3] Singh RK, Najmi AK, Dastidar SG.Biological functions and role of mitogen-activated protein kinase activated protein kinase 2 (MK2) in inflammatory diseases.Pharmacol Rep, 7,9(4):746-756.
    [4] Ruiz M, Coderre L, Allen BG, et al.Protecting the heart through MK2 modulation, toward a role in diabetic cardiomyopathy and lipid metabolism.Biochim Biophys Acta, 8,4(5 Pt B):1914-1922.
    [5] Fiore M, Forli S, Manetti F.Targeting mitogen-activated protein kinase-activated protein kinase 2 (MAPKAPK2, MK2):medicinal chemistry efforts to lead small molecule inhibitors to clinical trials.J Med Chem, 6,9(8):3609-3634.
    [6] Gurgis F M, Ziaziaris W, Munoz L.Mitogen-activated protein kinase-activated protein kinase 2 in neuroinflammation, heat shock protein 27 phosphorylation, and cell cycle:role and targeting.Mol Pharmacol, 4,5(2):345-356.
    [7] Gaestel M.What goes up must come down:molecular basis of MAPKAP kinase 2/3-dependent regulation of the inflammatory response and its inhibition.Biol Chem, 3,4(10):1301-1315.
    [8] Singh RK, Diwan M, Dastidar SG, et al.Differential effect of p38 and MK2 kinase inhibitors on the inflammatory and toxicity biomarkers in vitro.Hum Exp Toxicol, 8,7(5):521-531.
    [9] Limbourg A, Felden JV, Jagavelu K, et al.MAP-kinase activated protein kinase 2 links endothelial activation and monocyte/macrophage recruitment in arteriogenesis.Plos One, 5,0(10):e0138542.
    [10] Jagavelu K, Tietge UJ, Gaestel M, et al.Systemic deficiency of the MAP kinase-activated protein kinase 2 reduces atherosclerosis in hypercholesterolemic mice.Circ Res, 7,1(11):1104-1112.
    [11] Ebrahimian T, Li MW, Lemarié CA, et al.Mitogen-activated protein kinase-activated protein kinase 2 in angiotensin Ⅱ-induced inflammation and hypertension:regulation of oxidative stress.Hypertension, 1,7(2):245-254.
    [12] Wu W, Huang Q, Miao J, et al.MK2 plays an important role for the increased vascular permeability that follows thermal injury.Burns, 3,9(5):923-934.
    [13] Abhinand CS, Raju R, Soumya SJ, et al.VEGF-A/VEGFR2 signaling network in endothelial cells relevant to angiogenesis.J Cell Commun Signal, 6,0(4):1-8.
    [14] Kobayashi M, Nishita M, Mishima T, et al.MAPKAPK-2-mediated LIM-kinase activation is critical for VEGF-induced actin remodeling and cell migration.EMBO J, 6,5(4):713-726.
    [15] Butoi E, Gan AM, Tucureanu MM, et al.Cross-talk between macrophages and smooth muscle cells impairs collagen and metalloprotease synthesis and promotes angiogenesis.Biochim Biophys Acta, 6,3(7):1568-1578.
    [16] Jagielska J, Kapopara PR, Salguero G, et al.Interleukin-1 assembles a proangiogenic signaling module consisting of caveolin-1, tumor necrosis factor receptor-associated factor 6, p38-mitogen-activated protein kinase (MAPK), and MAPK-activated protein kinase 2 in endothelial cells.Arterioscler Thromb Vasc Biol, 2,2(5):1280-1288.
    [17] Kapopara PR, Von FJ, Soehnlein O, et al.Deficiency of MAPK-activated protein kinase 2 (MK2) prevents adverse remodelling and promotes endothelial healing after arterial injury.Thromb Haemost, 4,2(6):1264-1276.
    [18] Ashraf MI, Ebner M, Wallner C, et al.A p38MAPK/MK2 signaling pathway leading to redox stress, cell death and ischemia/reperfusion injury.Cell Commun Signal, 4,2(1):6-19.
    [19] Shiroto K, Otani H, Yamamoto F, et al.MK2－/－ gene knockout mouse hearts carry anti-apoptotic signal and are resistant to ischemia reperfusion injury.J Mol Cell Cardiol, 5,8(1):93-97.
    [20] Xu L, Yates CC, Lockyer P, et al.MMI-0100 inhibits cardiac fibrosis in myocardial infarction by direct actions on cardiomyocytes and fibroblasts via MK2 inhibition.J Mol Cell Cardiol, 4,7:86-101.
    [21] Brown DI, Cooley BC, Quintana MT, et al.Nebulized delivery of the MAPKAP kinase 2 peptide inhibitor MMI-0100 protects against ischemia-induced systolic dysfunction.Int J Pept Res Ther, 6,2(3):317-324.
    [22] Streicher JM, Ren S, Herschman H, et al.MAPK-activated protein kinase-2 in cardiac hypertrophy and cyclooxygenase-2 regulation in heart.Circ Res, 0,6(8):1434-1443.
    [23] Marks AR.Calcium cycling proteins and heart failure:mechanisms and therapeutics.J Clin Invest, 3,3(1):46-52.
    [24] Scharf M, Neef S, Freund R, et al.Mitogen-activated protein kinase-activated protein kinases 2 and 3 regulate SERCA2a expression and fiber type composition to modulate skeletal muscle and cardiomyocyte function.Mol Cell Biol, 3,3(13):2586-2602.
    [25] Schlapbach A, Huppertz C.Low-molecular-weight MK2 inhibitors:a tough nut to crack!.Future Med Chem, 9,1(7):1243-1257.
    [26] Fms G, kerfeldt MC, Heng B, et al.Cytotoxic activity of the MK2 inhibitor CMPD1 in glioblastoma cells is independent of MK2.Cell Death Discov, 5,1(1):15028-15039.
    [27] Huang X, Jr GWS, Cheng CC, et al.Discovery and hit-to-lead optimization of non-ATP competitive MK2 (MAPKAPK2) inhibitors.ACS Med Chem Lett, 1,2(8):632-637.
    [28] Xiao D, Zhu X, Sofolarides M, et al.Discovery of a novel series of potent MK2 non-ATP competitive inhibitors using 1,2-substituted azoles as cis-amide isosteres.Bioorg Med Chem Lett, 4,4(15):3609-3613.
    [29] Dong X, Palani A, Huang X, et al.Conformation constraint of anilides enabling the discovery of tricyclic lactams as potent MK2 non-ATP competitive inhibitors.Bioorg Med Chem Lett, 3,3(11):3262-3266.
    [30] Rao AU, Al EAE.ChemInform abstract:facile synthesis of tetracyclic azepine and oxazocine derivatives and their potential as MAPKAP-K2 (MK2) inhibitors.Bioorg Med Chem Lett, 2,2(2):1068-1072.
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CHEN Kun, ZUO Zhong, ZHAO Lei. Role of mitogen activated protein kinase activated protein kinase 2 in cardiovascular system[J]. Editorial Office of Chinese Journal of Arteriosclerosis,2019,27(5):456-460.

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History
  • Received:May 09,2018
  • Revised:August 30,2018
  • Online: April 08,2019
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