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Myofibroblasts and inflammatory cells as players of cardiac fibrosis

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Abstract

On myocardial infarction, many cells are injured or died owing to arterial occlusion. Intracellular molecules released from injured or dead cells initiate inflammatory responses that play important roles in cardiac remodeling including fibrosis. Fibrosis is an excess accumulation of extracellular collagen. Currently, drugs used to treat cardiac fibrosis are not commercially available. Myofibroblasts are responsible for the production and secretion of collagen. Infiltrating inflammatory cells interact with fibroblasts or other cells and promote myofibroblast formation. Inflammatory cells also modulate the activities of myofibroblasts. Regulation of collagen production is critical for modulating the progression of fibrosis. Hence, the manipulation of activities of inflammatory cells and myofibroblasts will provide promising therapeutic targets for treatment of cardiac fibrosis.

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References

  • Acharya A, Baek ST, Huang G, Eskiocak B, Goetsch S, Sung CY, Banfi S, Sauer MF, Olsen GS, Duffield JS, Olson EN, Tallquist MD (2012) The bHLH transcription factor Tcf21 Is required for lineage-specific EMT of cardiac fibroblast progenitors. Development 139:2139–2149

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Akhurst RJ, Padgett RW (2015) Matters of context guide future research in TGFβ superfamily signaling. Sci Signal 8:re10

    Article  PubMed  Google Scholar 

  • Ali SR, Ranjbarvaziri S, Talkhabi M, Zhao P, Subat A, Hojjat A, Kamran P, Müller AM, Volz KS, Tang Z, Red-Horse K, Ardehali R (2014) Developmental heterogeneity of cardiac fibroblasts does not predict pathological proliferation and activation. Circ Res 115:625–635

    Article  CAS  PubMed  Google Scholar 

  • Banerjee I, Fuseler JW, Price RL, Borg TK, Baudino TA (2007) Determination of cell types and numbers during cardiac development in the neonatal and adult rat and mouse. Am J Physiol Heart Circ Physiol 293:H1883–H1891

    Article  CAS  PubMed  Google Scholar 

  • Biernacka A, Frangogiannis NG (2011) Aging and cardiac fibrosis. Aging Dis 2:158–173

    PubMed  PubMed Central  Google Scholar 

  • Bochmann L, Sarathchandra P, Mori F, Lara-Pezzi E, Lazzaro D, Rosenthal N (2010) Revealing new mouse epicardial cell markers through transcriptomics. PLoS One 5:e11429

    Article  PubMed  PubMed Central  Google Scholar 

  • Braitsch CM, Kanisicak O, van Berlo JH, Molkentin JD, Yutzey KE (2013) Differential expression of embryonic epicardial progenitor markers and localization of cardiac fibrosis in adult ischemic injury and hypertensive heart disease. J Mol Cell Cardiol 65:108–119

    Article  CAS  PubMed  Google Scholar 

  • Campbell SE, Katwa LC (1997) Angiotensin II stimulated expression of transforming growth factor-beta1 in cardiac fibroblasts and myofibroblasts. J Mol Cell Cardiol 29:1947–1958

    Article  CAS  PubMed  Google Scholar 

  • Chao W (2009) Toll-like receptor signaling: a critical modulator of cell survival and ischemic injury in the heart. Am J Physiol Heart Circ Physiol 296:H1–H12

    Article  CAS  PubMed  Google Scholar 

  • Chong JJ, Reinecke H, Iwata M, Torok-Storb B, Stempien-Otero A, Murry CE (2013) Progenitor cells identified by PDGFR-alpha expression in the developing and diseased human heart. Stem Cells Dev 22:1932–1943

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Crean D, Cummins EP, Bahar B, Mohan H, McMorrow JP, Murphy EP (2015) Adenosine modulates NR4A orphan nuclear receptors to attenuate hyperinflammatory responses in monocytic cells. J Immunol 195:1436–1448

    Article  CAS  PubMed  Google Scholar 

  • Davis J, Burr AR, Davis GF, Birnbaumer L, Molkentin JD (2012) A TRPC6-dependent pathway for myofibroblast transdifferentiation and wound healing in vivo. Dev Cell 23:705–715

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deb A (2014) Cell–cell interaction in the heart via Wnt/β-catenin pathway after cardiac injury. Cardiovasc Res 102:214–223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Du J, Xie J, Zhang Z, Tsujikawa H, Fusco D, Silverman D, Liang B, Yue L (2010) TRPM7-mediated Ca2+ signals confer fibrogenesis in human atrial fibrillation. Circ Res 106:992–1003

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Dulauroy S, Di Carlo SE, Langa F, Eberl G, Peduto L (2012) Lineage tracing and genetic ablation of ADAM12(+) perivascular cells identify a major source of profibrotic cells during acute tissue injury. Nat Med 18:1262–1270

    Article  CAS  PubMed  Google Scholar 

  • Duprey P, Paulin D (1995) What can be learned from intermediate filament gene regulation in the mouse embryo. Int J Dev Biol 39:443–457

    CAS  PubMed  Google Scholar 

  • Engebretsen KV, Skårdal K, Bjørnstad S, Marstein HS, Skrbic B, Sjaastad I, Christensen G, Bjørnstad JL, Tønnessen T (2014) Attenuated development of cardiac fibrosis in left ventricular pressure overload by SM16, an orally active inhibitor of ALK5. J Mol Cell Cardiol 76:148–157

    Article  CAS  PubMed  Google Scholar 

  • Epelman S, Lavine KJ, Randolph GJ (2014) Origin and functions of tissue macrophages. Immunity 41:21–35

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang M, Xiang FL, Braitsch CM, Yutzey KE (2016) Epicardium-derived fibroblasts in heart development and disease. J Mol Cell Cardiol 91:23–27

    Article  CAS  PubMed  Google Scholar 

  • Francis Stuart SD, De Jesus NM, Lindsey ML, Ripplinger CM (2016) The crossroads of inflammation, fibrosis, and arrhythmia following myocardial infarction. J Mol Cell Cardiol 91:114–122

    Article  CAS  PubMed  Google Scholar 

  • Frantz S, Nahrendorf M (2014) Cardiac macrophages and their role in ischaemic heart disease. Cardiovasc Res 102:240–248

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Goldsmith EC, Hoffman A, Morales MO, Potts JD, Price RL, McFadden A, Rice M, Borg TK (2004) Organization of fibroblasts in the heart. Dev Dyn 230:787–794

    Article  CAS  PubMed  Google Scholar 

  • Gourdie RG, Dimmeler S, Kohl P (2016) Novel therapeutic strategies targeting fibroblasts and fibrosis in heart disease. Nat Rev Drug Discov. doi:10.1038/nrd.2016.89

    PubMed  Google Scholar 

  • Hartupee J, Mann DL (2016) Role of inflammatory cells in fibroblast activation. J Mol Cell Cardiol 93:143–148

    Article  CAS  PubMed  Google Scholar 

  • Haudek SB, Xia Y, Huebener P, Lee JM, Carlson S, Crawford JR, Pilling D, Gomer RH, Trial J, Frangogiannis NG, Entman ML (2006) Bone marrow-derived fibroblast precursors mediate ischemic cardiomyopathy in mice. Proc Natl Acad Sci USA 103:18284–18289

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Henderson NC, Arnold TD, Katamura Y, Giacomini MM, Rodriguez JD, McCarty JH, Pellicoro A, Raschperger E, Betsholtz C, Ruminski PG, Griggs DW, Prinsen MJ, Maher JJ, Iredale JP, Lacy-Hulbert A, Adams RH, Sheppard D (2013) Targeting of αv integrin identifies a core molecular pathway that regulates fibrosis in several organs. Nat Med 19:1617–1624

    Article  CAS  PubMed  Google Scholar 

  • Hilgendorf I, Gerhardt LM, Tan TC, Winter C, Holderried TA, Chousterman BG, Iwamoto Y, Liao R, Zirlik A, Scherer-Crosbie M, Hedrick CC, Libby P, Nahrendorf M, Weissleder R, Swirski FK (2014) Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium. Circ Res 114:1611–1622

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hinz B (2016) Myofibroblasts. Exp Eye Res 142:56–70

    Article  CAS  PubMed  Google Scholar 

  • Hofmann U, Frantz S (2016) Role of T-cells in myocardial infarction. Eur Heart J 37:873–879

    Article  PubMed  Google Scholar 

  • Hofmann U, Beyersdorf N, Weirather J, Podolskaya A, Bauersachs J, Ertl G, Kerkau T, Frantz S (2012) Activation of CD4+ T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice. Circulation 125:1652–1663

    Article  CAS  PubMed  Google Scholar 

  • Howangyin KY, Zlatanova I, Pinto C, Ngkelo A, Cochain C, Rouanet M, Vilar J, Lemitre M, Stockmann C, Fleischmann BK, Mallat Z, Silvestre JS (2016) Myeloid-epithelial-reproductive receptor tyrosine kinase and milk fat globule epidermal growth factor 8 coordinately improve remodeling after myocardial infarction via local delivery of vascular endothelial growth factor. Circulation 133:826–839

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hudon-David F, Bouzeghrane F, Couture P, Thibault G (2007) Thy-1 expression by cardiac fibroblasts: lack of association with myofibroblast contractile markers. J Mol Cell Cardiol 42:991–1000

    Article  CAS  PubMed  Google Scholar 

  • Kamo T, Akazawa H, Komuro I (2015) Cardiac nonmyocytes in the hub of cardiac hypertrophy. Circ Res 117:89–98

    Article  CAS  PubMed  Google Scholar 

  • Kaur H, Takefuji M, Ngai CY, Carvalho J, Bayer J, Wietelmann A, Poetsch A, Hoelper S, Conway SJ, Möllmann H, Looso M, Christian TroidlC, Offermanns S, Wettschureck N (2016) Targeted ablation of periostin-expressing activated fibroblasts prevents adverse cardiac remodeling in mice. Circ Res 118:1906–1917

    Article  CAS  PubMed  Google Scholar 

  • Kisseleva T, Cong M, Paik Y, Scholten D, Jiang C, Benner C, Iwaisako K, Moore-Morris T, Scott B, Tsukamoto H, Evans SM, Dillmann W, Glass CK, Brenner DA (2012) Myofibroblasts revert to an inactive phenotype during regression of liver fibrosis. Proc Natl Acad Sci USA 109:9448–9453

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kong P, Christia P, Saxena A, Su Y, Frangogiannis NG (2013) Lack of specificity of fibroblast-specific protein 1 in cardiac remodeling and fibrosis. Am J Physiol Heart Circ Physiol 305:H1363–H1372

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Krenning G, Zeisberg EM, Kalluri R (2010) The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol 225:631–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lane EB, Hogan BL, Kurkinen M, Garrels JI (1983) Co-expression of vimentin and cytokeratins in parietal endoderm cells of early mouse embryo. Nature 303:701–704

    Article  CAS  PubMed  Google Scholar 

  • Leask A (2015) Getting to the heart of the matter new insights into cardiac fibrosis. Circ Res 116:1269–1276

    Article  CAS  PubMed  Google Scholar 

  • Li L, Chen Y, Doan J, Murray J, Molkentin JD, Liu Q (2014) Transforming growth factor β-activated kinase 1 signaling pathway critically regulates myocardial survival and remodeling. Circulation 130:2162–2172

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Libby P, Nahrendorf M, Swirski FK (2015) Leukocytes link local and systemic inflammation in ischemic cardiovascular disease: an expanded “cardiovascular continuum”. J Am Coll Cardiol 67:1091–1103

    Article  Google Scholar 

  • Liu X, Ostrom RS, Insel PA (2004) cAMP-elevating agents and adenylyl cyclase overexpression promote an antifibrotic phenotype in pulmonary fibroblasts. Am J Physiol Cell Physiol 286:C1089–C1099

    Article  CAS  PubMed  Google Scholar 

  • Mantovani A, Biswas SK, Galdiero MR, Sica A, Locati M (2013) Macrophage plasticity and polarization in tissue repair and remodelling. J Pathol 229:176–185

    Article  CAS  PubMed  Google Scholar 

  • Moore-Morris T, Guimarães-Cambo N, Banerjee I, Zambon AC, Kisseleva T, Velayoudon A, Stallcup WB, Gu Y, Dalton ND, Cedenilla M, Gomez-Amaro R, Zhou B, Brenner DA, Peterson KL, Chen J, Evans SM (2014) Resident fibroblast lineages mediate pressure overload-induced cardiac fibrosis. J Clin Invest 124:2921–2934

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Moore-Morris T, Cattaneo P, Puceat M, Evans SM (2016) Origins of cardiac fibroblasts. J Mol Cell Cardiol 91:1–5

    Article  CAS  PubMed  Google Scholar 

  • Morales MO, Price RL, Goldsmith EC (2005) Expression of discoidin domain receptor 2 (DDR2) in the developing heart. Microsc Microanal 11:260–267

    Article  CAS  PubMed  Google Scholar 

  • Nanthakumar CB, Hatley RJ, Lemma S, Gauldie J, Marshall RP, Macdonald SJ (2015) Dissecting fibrosis: therapeutic insights from the small-molecule toolbox. Nat Rev Drug Discov 14:693–720

    Article  CAS  PubMed  Google Scholar 

  • Newby LK, Marber MS, Melloni C, Sarov-Blat L, Aberle LH, Aylward PE, Cai G, de Winter RJ, Hamm CW, Heitner JF, Kim R, Lerman A, Patel MR, Tanguay JF, Lepore JJ, Al-Khalidi HR, Sprecher DL, Granger CB, Investigators SOLSTICE (2014) Losmapimod, a novel p38 mitogen-activated protein kinase inhibitor, in non-ST-segment elevation myocardial infarction: a randomised phase 2 trial. Lancet 384:1187–1195

    Article  CAS  PubMed  Google Scholar 

  • Pei Y, Sherry DM, McDermott AM (2004) Thy-1 distinguishes human corneal fibroblasts and myofibroblasts from keratocytes. Exp Eye Res 79:705–712

    Article  CAS  PubMed  Google Scholar 

  • Piras BA, Tian Y, Xu Y, Thomas NA, O’Connor DM, French BA (2016) Systemic injection of AAV9 carrying a periostin promoter targets gene expression to a myofibroblast-like lineage in mouse hearts after reperfused myocardial infarction. Gene Ther 23:469–478

    Article  CAS  PubMed  Google Scholar 

  • Rahaman SO, Grove LM, Paruchuri S, Southern BD, Abraham S, Niese KA, Scheraga RG, Ghosh S, Thodeti CK, Zhang DX, Moran MM, Schilling WP, Tschumperlin DJ, Olman MA (2014) TRPV4 mediates myofibroblast differentiation and pulmonary fibrosis in mice. J Clin Invest 124:5225–5238

    Article  PubMed  PubMed Central  Google Scholar 

  • Reed NI, Jo H, Chen C, Tsujino K, Arnold TD, DeGrado WF, Sheppard D (2015) The αvβ1 integrin plays a critical in vivo role in tissue fibrosis. Sci Transl Med 7:288ra79

    Article  PubMed  PubMed Central  Google Scholar 

  • Reilkoff RA, Bucala R, Herzog EL (2011) Fibrocytes: emerging effector cells in chronic inflammation. Nat Rev Immunol 6:427–435

    Article  Google Scholar 

  • Rockey DC, Bell PD, Hill JA (2015) Fibrosis—a common pathway to organ injury and failure. New Eng J Med 372:1138–1149

    Article  CAS  PubMed  Google Scholar 

  • Rog-Zielinska EA, Norris RA, Kohl P, Markwald R (2016) The living scar—cardiac fibroblasts and the injured heart. Trends Mol Med 22:99–114

    Article  PubMed  Google Scholar 

  • Sassi Y, Ahles A, Truong DJ, Baqi Y, Lee SY, Husse B, Hulot JS, Foinquinos A, Thum T, Müller CE, Dendorfer A, Laggerbauer B, Engelhardt S (2014) Cardiac myocyte-secreted cAMP exerts paracrine action via adenosine receptor activation. J Clin Invest 124:5385–5397

    Article  PubMed  PubMed Central  Google Scholar 

  • Shimada YJ, Passeri JJ, Baggish AL, O’Callaghan C, Lowry PA, Yannekis G, Abbara S, Ghoshhajra BB, Rothman RD, Ho CY, Januzzi JL, Seidman CE, Fifer MA (2013) Effects of losartan on left ventricular hypertrophy and fibrosis in patients with nonobstructive hypertrophic cardiomyopathy. JACC Heart Fail 1:480–487

    Article  PubMed  PubMed Central  Google Scholar 

  • Skalli O, Ropraz P, Trzeciak A, Benzonana G, Gillessen D, Gabbiani G (1986) A monoclonal antibody against alpha-smooth muscle actin: a new probe for smooth muscle differentiation. J Cell Biol 103:2787–2796

    Article  CAS  PubMed  Google Scholar 

  • Smith CL, Baek ST, Sung CY, Tallquist MD (2011) Epicardial-derived cell epithelial-to-mesenchymal transition and fate specification require PDGF receptor signaling. Circ Res 108:e15–e26

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Strutz F, Okada H, Lo CW, Danoff T, Carone RL, Tomaszewski JE, Neilson EG (1955) Identification and characterization of a fibroblast marker: FSP1. J Cell Biol 130:393–405

    Article  Google Scholar 

  • Sun KH, Chang Y, Reed NI, Sheppard D (2016) αSMA is an inconsistent marker of fibroblasts responsible for force dependent TGFβ activation or collagen production across multiple models of organ fibrosis. Am J Physiol Lung Cell Mol Physiol 310:L824–L836

    Article  PubMed  Google Scholar 

  • Swirski FK, Nahrendorf M, Etzrodt M, Wildgruber M, Cortez-Retamozo V, Panizzi P, Figueiredo JL, Kohler RH, Chudnovskiy A, Waterman P, Aikawa E, Mempel TR, Libby P, Weissleder R, Pittet MJ (2009) Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science 325:612–616

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Swirski FK, Wildgruber M, Ueno T, Figueiredo JL, Panizzi P, Iwamoto Y, Zhang E, Stone JR, Rodriguez E, Chen JW, Pittet MJ, Weissleder R, Nahrendorf M (2010) Myeloperoxidase-rich Ly-6C+ myeloid cells infiltrate allografts and contribute to an imaging signature of organ rejection in mice. J Clin Invest 120:2627–2634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Thodeti CK, Paruchuri S, Meszaros JG (2013) A TRP to cardiac fibroblast differentiation. Channels 7:211–214

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Timmers L, Sluijter JP, van Keulen JK, Hoefer IE, Nederhoff MG, Goumans MJ, Doevendans PA, van Echteld CJ, Joles JA, Quax PH, Piek JJ, Pasterkamp G, de Kleijn DP (2008) Toll-like receptor 4 mediates maladaptive left ventricular remodeling and impairs cardiac function after myocardial infarction. Circ Res 102:257–264

    Article  CAS  PubMed  Google Scholar 

  • Timur F, Bolshakova G, Arutyunyan I, Elchaninov A, Makarov A, Kananykhina E, Khokhlova O, Murashev A, Glinkina V, Goldshtein D, Sukhikh G (2015) Bone marrow-derived multipotent stromal cells promote myocardial fibrosis and reverse remodeling of the left ventricle. Stem Cells Int 2015:746873

    Google Scholar 

  • Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC (2016) Cardiac fibrosis: the fibroblast awakens. Cir Res 118:1021–1040

    Article  CAS  Google Scholar 

  • Tsou PS, Haak AJ, Khanna D, Neubig RR (2014) Cellular mechanisms of tissue fibrosis. 8. Current and future drug targets in fibrosis: focus on Rho GTPase-regulated gene transcription. Am J Physiol Cell Physiol 307:C2–C13

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Turner NA (2016) Inflammatory and fibrotic responses of cardiac fibroblasts to myocardial damage associated molecular patterns (DAMPs). J Mol Cell Cardiol 94:189–200

    Article  CAS  PubMed  Google Scholar 

  • van Amerongen MJ, Harmsen MC, van Rooijen N, Petersen AH, van Luyn MJ (2007) Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice. Am J Pathol 170:818–829

    Article  PubMed  PubMed Central  Google Scholar 

  • van Amerongen MJ, Bou-Gharios G, Popa E, van Ark J, Petersen AH, van Dam GM, van Luyn MJ, Harmsen MC (2008) Bone marrow-derived myofibroblasts contribute functionally to scar formation after myocardial infarction. J Pathol 214:377–386

    Article  PubMed  Google Scholar 

  • Velasquez LS, Sutherland LB, Liu Z, Grinnell F, Kamm KE, Schneider JW, Olson EN, Small EM (2013) Activation of MRTF-A-dependent gene expression with a small molecule promotes myofibroblast differentiation and wound healing. Proc Natl Acad Sci USA 110:16850–16855

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wang YF, Hsu YJ, Wu HF, Lee GL, Yang YS, Wu JY, Yet SF, Wu KK, Cheng-Chin Kuo CC (2016) Endothelium-derived 5-methoxytryptophan is a circulating anti-inflammatory molecule that blocks systemic inflammation. Circ Res 119:222–236

    Article  CAS  PubMed  Google Scholar 

  • Wong SP, Rowley JE, Redpath AN, Tilman JD, Fellous TG, Johnson JR (2015) Pericytes, mesenchymal stem cells and their contributions to tissue repair. Pharmacol Ther 151:107–120

    Article  CAS  PubMed  Google Scholar 

  • Xia N, Jiao J, Tang TT, Lv BJ, Lu YZ, Wang KJ, Zhu ZF, Mao XB, Nie SF, Wang Q, Tu X, Xiao H, Liao YH, Shi GP, Cheng X (2015) Activated regulatory T-cells attenuate myocardial ischaemia/reperfusion injury through a CD39-dependent mechanism. Clin Sci 128:679–693

    Article  CAS  PubMed  Google Scholar 

  • Xue J, Schmidt SV, Sander J, Draffehn A, Krebs W, Quester I, De Nardo D, Gohel TD, Emde M, Schmidleithner L, Ganesan H, Nino-Castro A, Mallmann MR, Labzin L, Theis H, Kraut M, Beyer M, Latz E, Freeman TC, Ulas T, Schultze JL (2014) Transcriptome-based network analysis reveals a spectrum model of human macrophage activation. Immunity 40:274–288

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yan X, Anzai A, Katsumata Y, Matsuhashi T, Ito K, Endo J, Yamamoto T, Takeshima A, Shinmura K, Shen W, Fukuda K, Sano M (2013) Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction. J Mol Cell Cardiol 62:24–35

    Article  CAS  PubMed  Google Scholar 

  • Yao HW, Li J (2015) Epigenetic modifications in fibrotic diseases: implications for pathogenesis and pharmacological targets. J Pharmacol Exp Ther 352:2–13

    Article  PubMed  Google Scholar 

  • Yata Y, Scanga A, Gillan A, Yang L, Reif S, Breindl M, Brenner DA, Rippe RA (2003) DNase I-hypersensitive sites enhance alpha1(I) collagen gene expression in hepatic stellate cells. Hepatology 37:267–276

    Article  CAS  PubMed  Google Scholar 

  • Yokoyama U, Patel HH, Lai NC, Aroonsakool N, Roth DM, Insel PA (2008) The cyclic AMP effector Epac integrates pro- and anti-fibrotic signals. Proc Natl Acad Sci USA 105:6386–6391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zeisberg EM, Tarnavski O, Zeisberg M, Dorfman AL, McMullen JR, Gustafsson E, Chandraker A, Yuan X, Pu WT, Roberts AB, Neilson EG, Sayegh MH, Izumo S, Kalluri R (2007) Endothelial-to-mesenchymal transition contributes to cardiac fibrosis. Nat Med 13:952–961

    Article  CAS  PubMed  Google Scholar 

  • Zhang W, Lavine KJ, Epelman S, Evans SA, Weinheimer CJ, Barger PM, Mann DL (2015) Necrotic myocardial cells release damage-associated molecular patterns that provoke fibroblast activation in vitro and trigger myocardial inflammation and fibrosis in vivo. J Am Heart Assoc 4:e001993

    Article  PubMed  PubMed Central  Google Scholar 

  • Zouggari Y, Ait-Oufella H, Bonnin P, Simon T, Sage AP, Guérin C, Vilar J, Caligiuri G, Tsiantoulas D, Laurans L, Dumeau E, Kotti S, Bruneval P, Charo IF, Binder CJ, Danchin N, Tedgui A, Tedder TF, Silvestre JS, Mallat Z (2013) B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat Med 19:1273–1280

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgments

This work was supported by National Science and Technology Development Agency (NSTDA) Grant P-12-01409 and the Center of Excellence for Innovation in Drug Design and Discovery, Faculty of Pharmacy, Mahidol University to S. Mangmool, and by JSPS KAKENHI (25253011) and the Uehara Memorial Foundation to H. Kurose.

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  1. Department of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan

    Hitoshi Kurose

  2. Department of Pharmacology, Faculty of Pharmacy, Mahidol University, Bangkok, 10400, Thailand

    Supachoke Mangmool

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Correspondence to Hitoshi Kurose.

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Kurose, H., Mangmool, S. Myofibroblasts and inflammatory cells as players of cardiac fibrosis. Arch. Pharm. Res. 39, 1100–1113 (2016). https://doi.org/10.1007/s12272-016-0809-6

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