Cardiac fibrosis in myocardial infarction—from repair and remodeling to regeneration

Cell and Tissue Research

Volumn 365, Issue 3, 2016, Pages 563-581

  Talman, Virpi ^a   Ruskoaho, Heikki ^a  

^a UNIVERSITY OF HELSINKI   (Finland)

Author keywords

Anti fibrotic therapy; Cardiac fibrosis; Cardiac regeneration; Myocardial infarction; Pro fibrotic signaling

Indexed keywords

ALPHA SMOOTH MUSCLE ACTIN; ANGIOTENSIN; ANGIOTENSIN 1 RECEPTOR ANTAGONIST; COLLAGEN; CONNECTIVE TISSUE GROWTH FACTOR; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; ENDOTHELIN 1; FIBROBLAST GROWTH FACTOR; FIBRONECTIN; GAP JUNCTION PROTEIN; GELATINASE B; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INTERLEUKIN 1BETA; INTERLEUKIN 6; LONG UNTRANSLATED RNA; MATRIX METALLOPROTEINASE; MYOSIN; OSTEOPONTIN; PLATELET DERIVED GROWTH FACTOR; REACTIVE OXYGEN METABOLITE; SCLEROPROTEIN; TENASCIN; THROMBOSPONDIN; TISSUE INHIBITOR OF METALLOPROTEINASE; TOLL LIKE RECEPTOR; TRANSCRIPTION FACTOR RUNX2; TRANSFORMING GROWTH FACTOR BETA; TUMOR NECROSIS FACTOR; UNINDEXED DRUG;

CARDIAC MUSCLE CELL; CELL DIFFERENTIATION; CELL INTERACTION; CELL MATURATION; CELL MIGRATION; CELL PROLIFERATION; DOWN REGULATION; ENDOTHELIUM CELL; EPITHELIAL MESENCHYMAL TRANSITION; EXTRACELLULAR MATRIX; FIBROBLAST; FOCAL ADHESION; GENE EXPRESSION REGULATION; HEART FAILURE; HEART INFARCTION; HEART MUSCLE FIBROSIS; HUMAN; LEUKOCYTE; MACROPHAGE; MESENCHYME CELL; METABOLIC INHIBITION; MYOFIBROBLAST; NONHUMAN; NUCLEAR REPROGRAMMING; PERICYTE; PRIORITY JOURNAL; PROTEIN DEGRADATION; PROTEIN EXPRESSION; REVIEW; SIGNAL TRANSDUCTION; TISSUE REGENERATION; UPREGULATION; WOUND HEALING; ANIMAL; CARDIAC MUSCLE; FIBROSIS; PATHOLOGY; REGENERATION; VASCULAR REMODELING;

ANIMALS; FIBROSIS; HUMANS; MYOCARDIAL INFARCTION; MYOCARDIUM; REGENERATION; VASCULAR REMODELING; WOUND HEALING;

EID: 84975230737     PISSN: 0302766X     EISSN: 14320878     Source Type: Journal    
DOI: 10.1007/s00441-016-2431-9     Document Type: Review

References (151)

1. Addis RC, Ifkovits JL, Pinto F, Kellam LD, Esteso P, Rentschler S, Christoforou N, Epstein JA, Gearhart JD (2013) Optimization of direct fibroblast reprogramming to cardiomyocytes using calcium activity as a functional measure of success. J Mol Cell Cardiol 60:97–106
2. Ali SR, Ranjbarvaziri S, Talkhabi M, Zhao P, Subat A, Hojjat A, Kamran P, Muller 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
3. 2-Adrenergic receptor regulates cardiac fibroblast autophagy and collagen degradation. Biochim Biophys Acta 1812:23–31
4. Arslan F, Smeets MB, Riem Vis PW, Karper JC, Quax PH, Bongartz LG, Peters JH, Hoefer IE, Doevendans PA, Pasterkamp G, de Kleijn DP (2011) Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction. Circ Res 108:582–592
5. Aurora AB, Porrello ER, Tan W, Mahmoud AI, Hill JA, Bassel-Duby R, Sadek HA, Olson EN (2014) Macrophages are required for neonatal heart regeneration. J Clin Invest 124:1382–1392
6. Bader M (2010) Tissue renin-angiotensin-aldosterone systems: targets for pharmacological therapy. Annu Rev Pharmacol Toxicol 50:439–465
7. 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
8. Becker RO, Chapin S, Sherry R (1974) Regeneration of the ventricular myocardium in amphibians. Nature 248:145–147
9. Bui AL, Horwich TB, Fonarow GC (2011) Epidemiology and risk profile of heart failure. Nat Rev Cardiol 8:30–41
10. Bujak M, Ren G, Kweon HJ, Dobaczewski M, Reddy A, Taffet G, Wang XF, Frangogiannis NG (2007) Essential role of Smad3 in infarct healing and in the pathogenesis of cardiac remodeling. Circulation 116:2127–2138
11. Buscemi L, Ramonet D, Klingberg F, Formey A, Smith-Clerc J, Meister JJ, Hinz B (2011) The single-molecule mechanics of the latent TGF-β1 complex. Curr Biol 21:2046–2054
12. Care A, Catalucci D, Felicetti F, Bonci D, Addario A, Gallo P, Bang ML, Segnalini P, Gu Y, Dalton ND, Elia L, Latronico MV, Hoydal M, Autore C, Russo MA, Dorn GW II, Ellingsen O, Ruiz-Lozano P, Peterson KL, Croce CM, Peschle C, Condorelli G (2007) MicroRNA-133 controls cardiac hypertrophy. Nat Med 13:613–618
13. Carter RL, Grisanti LA, Yu JE, Repas AA, Woodall M, Ibetti J, Koch WJ, Jacobson MA, Tilley DG (2014) Dynamic mass redistribution analysis of endogenous β-adrenergic receptor signaling in neonatal rat cardiac fibroblasts. Pharmacol Res Perspect 2:e00024. doi:10.1002/prp2.24
14. Castoldi G, Di Gioia CR, Bombardi C, Catalucci D, Corradi B, Gualazzi MG, Leopizzi M, Mancini M, Zerbini G, Condorelli G, Stella A (2012) MiR-133a regulates collagen 1A1: potential role of miR-133a in myocardial fibrosis in angiotensin II-dependent hypertension. J Cell Physiol 227:850–856
15. Chen JX, Krane M, Deutsch MA, Wang L, Rav-Acha M, Gregoire S, Engels MC, Rajarajan K, Karra R, Abel ED, Wu JC, Milan D, Wu SM (2012) Inefficient reprogramming of fibroblasts into cardiomyocytes using Gata4, Mef2c, and Tbx5. Circ Res 111:50–55
16. Chen C, Li R, Ross RS, Manso AM (2016) Integrins and integrin-related proteins in cardiac fibrosis. J Mol Cell Cardiol 93:162–174. doi:10.1016/j.yjmcc.2015.11.010
17. Christoforou N, Chellappan M, Adler AF, Kirkton RD, Wu T, Addis RC, Bursac N, Leong KW (2013) Transcription factors MYOCD, SRF, Mesp1 and SMARCD3 enhance the cardio-inducing effect of GATA4, TBX5, and MEF2C during direct cellular reprogramming. PLoS One 8:e63577
18. Clowes C, Boylan MG, Ridge LA, Barnes E, Wright JA, Hentges KE (2014) The functional diversity of essential genes required for mammalian cardiac development. Genesis 52:713–737
19. Corinaldesi C, Di Luigi L, Lenzi A, Crescioli C (2016) Phosphodiesterase type 5 inhibitors: back and forward from cardiac indications. J Endocrinol Invest 39:143–151
20. Cunnington RH, Wang B, Ghavami S, Bathe KL, Rattan SG, Dixon IM (2011) Antifibrotic properties of c-Ski and its regulation of cardiac myofibroblast phenotype and contractility. Am J Physiol Cell Physiol 300:C176–C186
21. Dai Z, Aoki T, Fukumoto Y, Shimokawa H (2012) Coronary perivascular fibrosis is associated with impairment of coronary blood flow in patients with non-ischemic heart failure.J Cardiol 60:416–421
22. Davis J, Molkentin JD (2014) Myofibroblasts: trust your heart and let fate decide. J Mol Cell Cardiol 70:9–18
23. Deb A, Ubil E (2014) Cardiac fibroblast in development and wound healing. J Mol Cell Cardiol 70:47–55
24. Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G (1993) Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 122:103–111
25. Dobaczewski M, Bujak M, Li N, Gonzalez-Quesada C, Mendoza LH, Wang XF, Frangogiannis NG (2010) Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction. Circ Res 107:418–428
26. Dobaczewski M, Chen W, Frangogiannis NG (2011) Transforming growth factor (TGF)-β signaling in cardiac remodeling. J Mol Cell Cardiol 51:600–606
27. Dobaczewski M, de Haan JJ, Frangogiannis NG (2012) The extracellular matrix modulates fibroblast phenotype and function in the infarcted myocardium. J Cardiovasc Transl Res 5:837–847
28. Duan J, Gherghe C, Liu D, Hamlett E, Srikantha L, Rodgers L, Regan JN, Rojas M, Willis M, Leask A, Majesky M, Deb A (2012) Wnt1/β-catenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair. EMBO J 31:429–442
29. Efe JA, Hilcove S, Kim J, Zhou H, Ouyang K, Wang G, Chen J, Ding S (2011) Conversion of mouse fibroblasts into cardiomyocytes using a direct reprogramming strategy. Nat Cell Biol 13:215–222
30. Francis Stuart SD, De Jesus NM, Lindsey ML, Ripplinger CM (2015) The crossroads of inflammation, fibrosis, and arrhythmia following myocardial infarction. J Mol Cell Cardiol 91:114–122
31. Frangogiannis NG (2012) Matricellular proteins in cardiac adaptation and disease. Physiol Rev 92:635–688
32. Frangogiannis NG (2014) The inflammatory response in myocardial injury, repair, and remodelling. Nat Rev Cardiol 11:255–265
33. Fu JD, Srivastava D (2015) Direct reprogramming of fibroblasts into cardiomyocytes for cardiac regenerative medicine. Circ J 79:245–254
34. Fu JD, Stone NR, Liu L, Spencer CI, Qian L, Hayashi Y, Delgado-Olguin P, Ding S, Bruneau BG, Srivastava D (2013) Direct reprogramming of human fibroblasts toward a cardiomyocyte-like state. Stem Cell Rep 1:235–247
35. Fu Y, Huang C, Xu X, Gu H, Ye Y, Jiang C, Qiu Z, Xie X (2015) Direct reprogramming of mouse fibroblasts into cardiomyocytes with chemical cocktails. Cell Res 25:1013–1024
36. Furtado MB, Costa MW, Pranoto EA, Salimova E, Pinto AR, Lam NT, Park A, Snider P, Chandran A, Harvey RP, Boyd R, Conway SJ, Pearson J, Kaye DM, Rosenthal NA (2014) Cardiogenic genes expressed in cardiac fibroblasts contribute to heart development and repair. Circ Res 114:1422–1434
37. Galindo CL, Kasasbeh E, Murphy A, Ryzhov S, Lenihan S, Ahmad FA, Williams P, Nunnally A, Adcock J, Song Y, Harrell FE, Tran TL, Parry TJ, Iaci J, Ganguly A, Feoktistov I, Stephenson MK, Caggiano AO, Sawyer DB, Cleator JH (2014) Anti-remodeling and anti-fibrotic effects of the neuregulin-1β glial growth factor 2 in a large animal model of heart failure. J Am Heart Assoc 3:e000773
38. Gherghiceanu M, Barad L, Novak A, Reiter I, Itskovitz-Eldor J, Binah O, Popescu LM (2011) Cardiomyocytes derived from human embryonic and induced pluripotent stem cells: comparative ultrastructure. J Cell Mol Med 15:2539–2551
39. Gong W, Yan M, Chen J, Chaugai S, Chen C, Wang D (2014) Chronic inhibition of cyclic guanosine monophosphate-specific phosphodiesterase 5 prevented cardiac fibrosis through inhibition of transforming growth factor β-induced Smad signaling. Front Med 8:445–455
40. Gonzalez-Rosa JM, Peralta M, Mercader N (2012) Pan-epicardial lineage tracing reveals that epicardium derived cells give rise to myofibroblasts and perivascular cells during zebrafish heart regeneration. Dev Biol 370:173–186
41. Gonzalez-Santamaria J, Villalba M, Busnadiego O, Lopez-Olaneta MM, Sandoval P, Snabel J, Lopez-Cabrera M, Erler JT, Hanemaaijer R, Lara-Pezzi E, Rodriguez-Pascual F (2016) Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction. Cardiovasc Res 109:67–78
42. Gulati A, Jabbour A, Ismail TF, Guha K, Khwaja J, Raza S, Morarji K, Brown TD, Ismail NA, Dweck MR, Di Pietro E, Roughton M, Wage R, Daryani Y, O’Hanlon R, Sheppard MN, Alpendurada F, Lyon AR, Cook SA, Cowie MR, Assomull RG, Pennell DJ, Prasad SK (2013) Association of fibrosis with mortality and sudden cardiac death in patients with nonischemic dilated cardiomyopathy. JAMA 309:896–908
43. Harvey RP, Wystub-Lis K, Del Monte-Nieto G, Graham RM, Tzahor E (2016) Cardiac regeneration therapies—targeting neuregulin 1 signalling. Heart Lung Circ 25:4–7
44. Hayashidani S, Tsutsui H, Shiomi T, Suematsu N, Kinugawa S, Ide T, Wen J, Takeshita A (2002) Fluvastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, attenuates left ventricular remodeling and failure after experimental myocardial infarction. Circulation 105:868–873
45. Heineke J, Molkentin JD (2006) Regulation of cardiac hypertrophy by intracellular signalling pathways. Nat Rev Mol Cell Biol 7:589–600
46. Hermans KC, Daskalopoulos EP, Blankesteijn WM (2012) Interventions in Wnt signaling as a novel therapeutic approach to improve myocardial infarct healing. Fibrogenesis Tissue Repair 5:16
47. Hermida N, Markl A, Hamelet J, Van Assche T, Vanderper A, Herijgers P, van Bilsen M, Hilfiker-Kleiner D, Noppe G, Beauloye C, Horman S, Balligand JL (2013) HMGCoA reductase inhibition reverses myocardial fibrosis and diastolic dysfunction through AMP-activated protein kinase activation in a mouse model of metabolic syndrome. Cardiovasc Res 99:44–54
48. Hirai H, Katoku-Kikyo N, Keirstead SA, Kikyo N (2013) Accelerated direct reprogramming of fibroblasts into cardiomyocyte-like cells with the MyoD transactivation domain. Cardiovasc Res 100:105–113
49. Horn MA, Trafford AW (2016) Aging and the cardiac collagen matrix: novel mediators of fibrotic remodelling. J Mol Cell Cardiol 93:175–185. doi:10.1016/j.yjmcc.2015.11.005
50. Ieda M, Fu JD, Delgado-Olguin P, Vedantham V, Hayashi Y, Bruneau BG, Srivastava D (2010) Direct reprogramming of fibroblasts into functional cardiomyocytes by defined factors. Cell 142:375–386
51. Ifkovits JL, Addis RC, Epstein JA, Gearhart JD (2014) Inhibition of TGFβ signaling increases direct conversion of fibroblasts to induced cardiomyocytes. PLoS One 9:e89678
52. Jaffer FA, Sosnovik DE, Nahrendorf M, Weissleder R (2006) Molecular imaging of myocardial infarction. J Mol Cell Cardiol 41:921–933
53. Jayawardena TM, Egemnazarov B, Finch EA, Zhang L, Payne JA, Pandya K, Zhang Z, Rosenberg P, Mirotsou M, Dzau VJ (2012) MicroRNA-mediated in vitro and in vivo direct reprogramming of cardiac fibroblasts to cardiomyocytes. Circ Res 110:1465–1473
54. Jayawardena T, Mirotsou M, Dzau VJ (2014) Direct reprogramming of cardiac fibroblasts to cardiomyocytes using microRNAs. Methods Mol Biol 1150:263–272
55. Jayawardena TM, Finch EA, Zhang L, Zhang H, Hodgkinson CP, Pratt RE, Rosenberg PB, Mirotsou M, Dzau VJ (2015) MicroRNA induced cardiac reprogramming in vivo: evidence for mature cardiac myocytes and improved cardiac function. Circ Res 116:418–424
56. Jopling C, Sleep E, Raya M, Marti M, Raya A, Izpisua Belmonte JC (2010) Zebrafish heart regeneration occurs by cardiomyocyte dedifferentiation and proliferation. Nature 464:606–609
57. Karakikes I, Chaanine AH, Kang S, Mukete BN, Jeong D, Zhang S, Hajjar RJ, Lebeche D (2013) Therapeutic cardiac-targeted delivery of miR-1 reverses pressure overload-induced cardiac hypertrophy and attenuates pathological remodeling. J Am Heart Assoc 2:e000078
58. Kass DA (2012) Cardiac role of cyclic-GMP hydrolyzing phosphodiesterase type 5: from experimental models to clinical trials. Curr Heart Fail Rep 9:192–199
59. + cardiomyocytes. Nature 464:601–605
60. Kim JS, Choi IG, Lee BC, Park JB, Kim JH, Jeong JH, Jeong JH, Seo CH (2012) Neuregulin induces CTGF expression in hypertrophic scarring fibroblasts. Mol Cell Biochem 365:181–189
61. Klingberg F, Hinz B, White ES (2013) The myofibroblast matrix: implications for tissue repair and fibrosis. J Pathol 229:298–309
62. Kohan DE, Cleland JG, Rubin LJ, Theodorescu D, Barton M (2012) Clinical trials with endothelin receptor antagonists: what went wrong and where can we improve? Life Sci 91:528–539
63. Kohl P, Gourdie RG (2014) Fibroblast-myocyte electrotonic coupling: does it occur in native cardiac tissue? J Mol Cell Cardiol 70:37–46
64. Kong P, Christia P, Frangogiannis NG (2014) The pathogenesis of cardiac fibrosis. Cell Mol Life Sci 71:549–574
65. + progenitors are key contributors to injury-induced organ fibrosis. Cell Stem Cell 16:51–66
66. Krenning G, Zeisberg EM, Kalluri R (2010) The origin of fibroblasts and mechanism of cardiac fibrosis. J Cell Physiol 225:631–637
67. Laflamme MA, Murry CE (2005) Regenerating the heart. Nat Biotechnol 23:845–856
68. Lajiness JD, Conway SJ (2014) Origin, development, and differentiation of cardiac fibroblasts. J Mol Cell Cardiol 70:2–8
69. Lalit PA, Salick MR, Nelson DO, Squirrell JM, Shafer CM, Patel NG, Saeed I, Schmuck EG, Markandeya YS, Wong R, Lea MR, Eliceiri KW, Hacker TA, Crone WC, Kyba M, Garry DJ, Stewart R, Thomson JA, Downs KM, Lyons GE, Kamp TJ (2016) Lineage reprogramming of fibroblasts into proliferative induced cardiac progenitor cells by defined factors. Cell Stem Cell 18:354–367
70. Leask A (2010) Potential therapeutic targets for cardiac fibrosis: TGFβ, angiotensin, endothelin, CCN2, and PDGF, partners in fibroblast activation. Circ Res 106:1675–1680
71. Leask A (2015) Getting to the heart of the matter: new insights into cardiac fibrosis. Circ Res 116:1269–1276
72. Lee CY, Burnett JC Jr (2007) Natriuretic peptides and therapeutic applications. Heart Fail Rev 12:131–142
73. Lighthouse JK, Small EM (2016) Transcriptional control of cardiac fibroblast plasticity. J Mol Cell Cardiol 91:52–60
74. Lindsey ML, Iyer RP, Jung M, DeLeon-Pennell KY, Ma Y (2016) Matrix metalloproteinases as input and output signals for post-myocardial infarction remodeling. J Mol Cell Cardiol 91:134–140
75. Luna-Zurita L, Stirnimann CU, Glatt S, Kaynak BL, Thomas S, Baudin F, Samee MA, He D, Small EM, Mileikovsky M, Nagy A, Holloway AK, Pollard KS, Muller CW, Bruneau BG (2016) Complex interdependence regulates heterotypic transcription factor distribution and coordinates cardiogenesis. Cell 164:999–1014
76. Lynch JM, Maillet M, Vanhoutte D, Schloemer A, Sargent MA, Blair NS, Lynch KA, Okada T, Aronow BJ, Osinska H, Prywes R, Lorenz JN, Mori K, Lawler J, Robbins J, Molkentin JD (2012) A thrombospondin-dependent pathway for a protective ER stress response. Cell 149:1257–1268
77. Ma H, Wang L, Yin C, Liu J, Qian L (2015) In vivo cardiac reprogramming using an optimal single polycistronic construct. Cardiovasc Res 108:217–219
78. Mathison M, Singh VP, Gersch RP, Ramirez MO, Cooney A, Kaminsky SM, Chiuchiolo MJ, Nasser A, Yang J, Crystal RG, Rosengart TK (2014) “Triplet” polycistronic vectors encoding Gata4, Mef2c, and Tbx5 enhances postinfarct ventricular functional improvement compared with singlet vectors. J Thorac Cardiovasc Surg 148:1656–1664
79. Matkovich SJ, Wang W, Tu Y, Eschenbacher WH, Dorn LE, Condorelli G, Diwan A, Nerbonne JM, Dorn GW II (2010) MicroRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts. Circ Res 106:166–175
80. McMurray JJ, Adamopoulos S, Anker SD, Auricchio A, Bohm M, Dickstein K, Falk V, Filippatos G, Fonseca C, Gomez-Sanchez MA, Jaarsma T, Kober L, Lip GY, Maggioni AP, Parkhomenko A, Pieske BM, Popescu BA, Ronnevik PK, Rutten FH, Schwitter J, Seferovic P, Stepinska J, Trindade PT, Voors AA, Zannad F, Zeiher A, ESC Committee for Practice Guidelines (2012) ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2012: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2012 of the European Society of Cardiology. Eur Heart J 33:1787–1847
81. Moilanen AM, Rysä J, Mustonen E, Serpi R, Aro J, Tokola H, Leskinen H, Manninen A, Levijoki J, Vuolteenaho O, Ruskoaho H (2011) Intramyocardial BNP gene delivery improves cardiac function through distinct context-dependent mechanisms. Circ Heart Fail 4:483–495
82. Moilanen AM, Rysä J, Serpi R, Mustonen E, Szabo Z, Aro J, Napankangas J, Tenhunen O, Sutinen M, Salo T, Ruskoaho H (2012) (Pro)renin receptor triggers distinct angiotensin II-independent extracellular matrix remodeling and deterioration of cardiac function. PLoS One 7:e41404
83. Möllmann H, Nef HM, Kostin S, von Kalle C, Pilz I, Weber M, Schaper J, Hamm CW, Elsasser A (2006) Bone marrow-derived cells contribute to infarct remodelling. Cardiovasc Res 71:661–671
84. Moore-Morris T, Guimaraes-Camboa 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
85. Moore-Morris T, Cattaneo P, Puceat M, Evans SM (2016) Origins of cardiac fibroblasts. J Mol Cell Cardiol 91:1–5
86. Mueller EE, Momen A, Masse S, Zhou YQ, Liu J, Backx PH, Henkelman RM, Nanthakumar K, Stewart DJ, Husain M (2011) Electrical remodelling precedes heart failure in an endothelin-1-induced model of cardiomyopathy. Cardiovasc Res 89:623–633
87. Muraoka N, Ieda M (2014) Direct reprogramming of fibroblasts into myocytes to reverse fibrosis. Annu Rev Physiol 76:21–37
88. Muraoka N, Yamakawa H, Miyamoto K, Sadahiro T, Umei T, Isomi M, Nakashima H, Akiyama M, Wada R, Inagawa K, Nishiyama T, Kaneda R, Fukuda T, Takeda S, Tohyama S, Hashimoto H, Kawamura Y, Goshima N, Aeba R, Yamagishi H, Fukuda K, Ieda M (2014) MiR-133 promotes cardiac reprogramming by directly repressing Snai1 and silencing fibroblast signatures. EMBO J 33:1565–1581
89. Mustonen E, Aro J, Puhakka J, Ilves M, Soini Y, Leskinen H, Ruskoaho H, Rysä J (2008) Thrombospondin-4 expression is rapidly upregulated by cardiac overload. Biochem Biophys Res Commun 373:186–191
90. Mustonen E, Ruskoaho H, Rysä J (2012) Thrombospondin-4, tumour necrosis factor-like weak inducer of apoptosis (TWEAK) and its receptor Fn14: novel extracellular matrix modulating factors in cardiac remodelling. Ann Med 44:793–804
91. Mustonen E, Ruskoaho H, Rysä J (2013) Thrombospondins, potential drug targets for cardiovascular diseases. Basic Clin Pharmacol Toxicol 112:4–12
92. Nam YJ, Song K, Luo X, Daniel E, Lambeth K, West K, Hill JA, DiMaio JM, Baker LA, Bassel-Duby R, Olson EN (2013) Reprogramming of human fibroblasts toward a cardiac fate. Proc Natl Acad Sci U S A 110:5588–5593
93. Nam YJ, Lubczyk C, Bhakta M, Zang T, Fernandez-Perez A, McAnally J, Bassel-Duby R, Olson EN, Munshi NV (2014) Induction of diverse cardiac cell types by reprogramming fibroblasts with cardiac transcription factors. Development 141:4267–4278
94. Nguyen G (2011) Renin, (pro)renin and receptor: an update. Clin Sci (Lond) 120:169–178
95. Nishioka T, Onishi K, Shimojo N, Nagano Y, Matsusaka H, Ikeuchi M, Ide T, Tsutsui H, Hiroe M, Yoshida T, Imanaka-Yoshida K (2010) Tenascin-C may aggravate left ventricular remodeling and function after myocardial infarction in mice. Am J Physiol Heart Circ Physiol 298:H1072–H1078
96. Oie E, Yndestad A, Robins SP, Bornerheim R, Asberg A, Attramadal H (2002) Early intervention with a potent endothelin-A/endothelin-B receptor antagonist aggravates left ventricular remodeling after myocardial infarction in rats. Basic Res Cardiol 97:239–247
97. Ongstad E, Kohl P (2016) Fibroblast-myocyte coupling in the heart: potential relevance for therapeutic interventions. J Mol Cell Cardiol 91:238–246
98. Palazzolo G, Quattrocelli M, Toelen J, Dominici R, Anastasia L, Tettamenti G, Barthelemy I, Blot S, Gijsbers R, Cassano M, Sampaolesi M (2016) Cardiac niche influences the direct reprogramming of canine fibroblasts into cardiomyocyte-like cells. Stem Cells Int 2016:4969430
99. Piccoli MT, Bar C, Thum T (2016) Non-coding RNAs as modulators of the cardiac fibroblast phenotype. J Mol Cell Cardiol 92:75–81
100. Pikkarainen S, Tokola H, Kerkelä R, Ruskoaho H (2004) GATA transcription factors in the developing and adult heart. Cardiovasc Res 63:196–207
101. Pinto AR, Ilinykh A, Ivey MJ, Kuwabara JT, D’Antoni M, Debuque RJ, Chandran A, Wang L, Arora K, Rosenthal N, Tallquist MD (2015) Revisiting cardiac cellular composition. Circ Res 118:400–409
102. Porrello ER, Mahmoud AI, Simpson E, Hill JA, Richardson JA, Olson EN, Sadek HA (2011) Transient regenerative potential of the neonatal mouse heart. Science 331:1078–1080
103. Porter KE, Turner NA (2009) Cardiac fibroblasts: at the heart of myocardial remodeling. Pharmacol Ther 123:255–278
104. Poss KD, Wilson LG, Keating MT (2002) Heart regeneration in zebrafish. Science 298:2188–2190
105. + cardiac progenitor cells. Stem Cells Dev 24:2622–2633
106. Protze S, Khattak S, Poulet C, Lindemann D, Tanaka EM, Ravens U (2012) A new approach to transcription factor screening for reprogramming of fibroblasts to cardiomyocyte-like cells. J Mol Cell Cardiol 53:323–332
107. Qian L, Huang Y, Spencer CI, Foley A, Vedantham V, Liu L, Conway SJ, Fu JD, Srivastava D (2012) In vivo reprogramming of murine cardiac fibroblasts into induced cardiomyocytes. Nature 485:593–598
108. Ripplinger CM, Lou Q, Li W, Hadley J, Efimov IR (2009) Panoramic imaging reveals basic mechanisms of induction and termination of ventricular tachycardia in rabbit heart with chronic infarction: implications for low-voltage cardioversion. Heart Rhythm 6:87–97
109. Rodriguez-Pascual F, Busnadiego O, Gonzalez-Santamaria J (2014) The profibrotic role of endothelin-1: is the door still open for the treatment of fibrotic diseases? Life Sci 118:156–164
110. Rosenkranz S (2004) TGF-β1 and angiotensin networking in cardiac remodeling. Cardiovasc Res 63:423–432
111. Roush S, Slack FJ (2008) The let-7 family of microRNAs. Trends Cell Biol 18:505–516
112. Ruiz-Villalba A, Simon AM, Pogontke C, Castillo MI, Abizanda G, Pelacho B, Sanchez-Dominguez R, Segovia JC, Prosper F, Perez-Pomares JM (2015) Interacting resident epicardium-derived fibroblasts and recruited bone marrow cells form myocardial infarction scar. J Am Coll Cardiol 65:2057–2066
113. Ruskoaho H (1992) Atrial natriuretic peptide: synthesis, release, and metabolism. Pharmacol Rev 44:479–602
114. Russell JL, Goetsch SC, Gaiano NR, Hill JA, Olson EN, Schneider JW (2011) A dynamic Notch injury response activates epicardium and contributes to fibrosis repair. Circ Res 108:51–59
115. Rysä J, Tenhunen O, Serpi R, Soini Y, Nemer M, Leskinen H, Ruskoaho H (2010) GATA-4 is an angiogenic survival factor of the infarcted heart. Circ Heart Fail 3:440–450
116. Sahara M, Santoro F, Chien KR (2015) Programming and reprogramming a human heart cell. EMBO J 34:710–738
117. Saxena A, Chen W, Su Y, Rai V, Uche OU, Li N, Frangogiannis NG (2013) IL-1 induces proinflammatory leukocyte infiltration and regulates fibroblast phenotype in the infarcted myocardium. J Immunol 191:4838–4848
118. Schuetze KB, McKinsey TA, Long CS (2014) Targeting cardiac fibroblasts to treat fibrosis of the heart: focus on HDACs. J Mol Cell Cardiol 70:100–107
119. Serini G, Bochaton-Piallat ML, Ropraz P, Geinoz A, Borsi L, Zardi L, Gabbiani G (1998) The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-β1. J Cell Biol 142:873–881
120. + cells, proliferation and apoptosis in the left ventricle after myocardial infarction. Clin Transl Sci 2:422–430
121. Shan H, Zhang Y, Lu Y, Zhang Y, Pan Z, Cai B, Wang N, Li X, Feng T, Hong Y, Yang B (2009) Downregulation of miR-133 and miR-590 contributes to nicotine-induced atrial remodelling in canines. Cardiovasc Res 83:465–472
122. Shinde AV, Frangogiannis NG (2014) Fibroblasts in myocardial infarction: a role in inflammation and repair. J Mol Cell Cardiol 70:74–82
123. Song K, Nam YJ, Luo X, Qi X, Tan W, Huang GN, Acharya A, Smith CL, Tallquist MD, Neilson EG, Hill JA, Bassel-Duby R, Olson EN (2012) Heart repair by reprogramming non-myocytes with cardiac transcription factors. Nature 485:599–604
124. Souders CA, Bowers SL, Baudino TA (2009) Cardiac fibroblast: the renaissance cell. Circ Res 105:1164–1176
125. Srivastava D, Berry EC (2013) Cardiac reprogramming: from mouse toward man. Curr Opin Genet Dev 23:574–578
126. Srivastava D, Yu P (2015) Recent advances in direct cardiac reprogramming. Curr Opin Genet Dev 34:77–81
127. Sun F, Duan W, Zhang Y, Zhang L, Qile M, Liu Z, Qiu F, Zhao D, Lu Y, Chu W (2015) Simvastatin alleviates cardiac fibrosis induced by infarction via up-regulation of TGF-β receptor III expression. Br J Pharmacol 172:3779–3792
128. Sutton MG, Sharpe N (2000) Left ventricular remodeling after myocardial infarction: pathophysiology and therapy. Circulation 101:2981–2988
129. Szabo Z, Magga J, Alakoski T, Ulvila J, Piuhola J, Vainio L, Kivirikko KI, Vuolteenaho O, Ruskoaho H, Lipson KE, Signore P, Kerkelä R (2014) Connective tissue growth factor inhibition attenuates left ventricular remodeling and dysfunction in pressure overload-induced heart failure. Hypertension 63:1235–1240
130. Talkhabi M, Pahlavan S, Aghdami N, Baharvand H (2015) Ascorbic acid promotes the direct conversion of mouse fibroblasts into beating cardiomyocytes. Biochem Biophys Res Commun 463:699–705
131. Tamura N, Ogawa Y, Chusho H, Nakamura K, Nakao K, Suda M, Kasahara M, Hashimoto R, Katsuura G, Mukoyama M, Itoh H, Saito Y, Tanaka I, Otani H, Katsuki M (2000) Cardiac fibrosis in mice lacking brain natriuretic peptide. Proc Natl Acad Sci U S A 97:4239–4244
132. Thum T (2014) Noncoding RNAs and myocardial fibrosis. Nat Rev Cardiol 11:655–663
133. Tolonen AM, Magga J, Szabo Z, Viitala P, Gao E, Moilanen AM, Ohukainen P, Vainio L, Koch WJ, Kerkelä R, Ruskoaho H, Serpi R (2014) Inhibition of Let-7 microRNA attenuates myocardial remodeling and improves cardiac function postinfarction in mice. Pharmacol Res Perspect 2:e00056
134. Tsuruda T, Boerrigter G, Huntley BK, Noser JA, Cataliotti A, Costello-Boerrigter LC, Chen HH, Burnett JC Jr (2002) Brain natriuretic peptide is produced in cardiac fibroblasts and induces matrix metalloproteinases. Circ Res 91:1127–1134
135. 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
136. van den Borne SW, Diez J, Blankesteijn WM, Verjans J, Hofstra L, Narula J (2010) Myocardial remodeling after infarction: the role of myofibroblasts. Nat Rev Cardiol 7:30–37
137. Vanhoutte D, Heymans S (2010) TIMPs and cardiac remodeling: “embracing the MMP-independent-side of the family”. J Mol Cell Cardiol 48:445–453
138. Visconti RP, Markwald RR (2006) Recruitment of new cells into the postnatal heart: potential modification of phenotype by periostin. Ann N Y Acad Sci 1080:19–33
139. Wada R, Muraoka N, Inagawa K, Yamakawa H, Miyamoto K, Sadahiro T, Umei T, Kaneda R, Suzuki T, Kamiya K, Tohyama S, Yuasa S, Kokaji K, Aeba R, Yozu R, Yamagishi H, Kitamura T, Fukuda K, Ieda M (2013) Induction of human cardiomyocyte-like cells from fibroblasts by defined factors. Proc Natl Acad Sci U S A 110:12667–12672
140. Wang Y, Ait-Oufella H, Herbin O, Bonnin P, Ramkhelawon B, Taleb S, Huang J, Offenstadt G, Combadiere C, Renia L, Johnson JL, Tharaux PL, Tedgui A, Mallat Z (2010) TGF-β activity protects against inflammatory aortic aneurysm progression and complications in angiotensin II-infused mice. J Clin Invest 120:422–432
141. Wang H, Cao N, Spencer CI, Nie B, Ma T, Xu T, Zhang Y, Wang X, Srivastava D, Ding S (2014) Small molecules enable cardiac reprogramming of mouse fibroblasts with a single factor, Oct4. Cell Rep 6:951–960
142. Wang L, Liu Z, Yin C, Asfour H, Chen O, Li Y, Bursac N, Liu J, Qian L (2015) Stoichiometry of Gata4, Mef2c, and Tbx5 influences the efficiency and quality of induced cardiac myocyte reprogramming. Circ Res 116:237–244
143. Weber KT, Sun Y, Bhattacharya SK, Ahokas RA, Gerling IC (2013) Myofibroblast-mediated mechanisms of pathological remodelling of the heart. Nat Rev Cardiol 10:15–26
144. Willems IE, Havenith MG, De Mey JG, Daemen MJ (1994) The α-smooth muscle actin-positive cells in healing human myocardial scars. Am J Pathol 145:868–875
145. Zeisberg EM, Kalluri R (2010) Origins of cardiac fibroblasts. Circ Res 107:1304–1312
146. 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
147. Zhang Y, Cao N, Huang Y, Spencer CI, Fu JD, Yu C, Liu K, Nie B, Xu T, Li K, Xu S, Bruneau BG, Srivastava D, Ding S (2016) Expandable cardiovascular progenitor cells reprogrammed from fibroblasts. Cell Stem Cell 18:368–381
148. Zhao W, Zhao T, Huang V, Chen Y, Ahokas RA, Sun Y (2011) Platelet-derived growth factor involvement in myocardial remodeling following infarction. J Mol Cell Cardiol 51:830–838
149. Zhao Y, Londono P, Cao Y, Sharpe EJ, Proenza C, O’Rourke R, Jones KL, Jeong MY, Walker LA, Buttrick PM, McKinsey TA, Song K (2015) High-efficiency reprogramming of fibroblasts into cardiomyocytes requires suppression of pro-fibrotic signalling. Nat Commun 6:8243
150. Zhou H, Dickson ME, Kim MS, Bassel-Duby R, Olson EN (2015) Akt1/protein kinase B enhances transcriptional reprogramming of fibroblasts to functional cardiomyocytes. Proc Natl Acad Sci U S A 112:11864–11869
151. Zhou Y, Wang L, Vaseghi HR, Liu Z, Lu R, Alimohamadi S, Yin C, Fu JD, Wang GG, Liu J, Qian L (2016) Bmi1 is a key epigenetic barrier to direct cardiac reprogramming. Cell Stem Cell 18:382–395