Single-target RNA interference for the blockade of multiple interacting proinflammatory and profibrotic pathways in cardiac fibroblasts

Journal of Molecular and Cellular Cardiology

Volumn 66, Issue , 2014, Pages 141-156

  Tank, Juliane ^a   Lindner, Diana ^a,e   Wang, Xiaomin ^a   Stroux, Andrea ^a   Gilke, Leona ^a   Gast, Martina ^a   Zietsch, Christin ^a   Skurk, Carsten ^a   Scheibenbogen, Carmen ^b   Klingel, Karin ^d   Lassner, Dirk ^c   Kühl, Uwe ^a   Schultheiss, Heinz Peter ^a   Westermann, Dirk ^a   Poller, Wolfgang ^a,b  

^a Department of Psychiatry   (Germany)

^b CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

^c Institute of Cardiac Diagnostics and Therapy   (Germany)

^d UNIVERSITY HOSPITAL TÜBINGEN   (Germany)

^e UNIVERSITY HEART CENTER HAMBURG   (Germany)

Author keywords

Fibrosis; Heart disease; Immuno therapy; Inflammation; Remodeling; RNA interference

Indexed keywords

ADENOVIRUS VECTOR; CCN PROTEIN; CONNECTIVE TISSUE GROWTH FACTOR; CONNEXIN 43; GELATINASE A; GELATINASE B; MICRORNA; MICRORNA 133B; MICRORNA 30C; MONOCYTE CHEMOTACTIC PROTEIN 1; MONOCYTE CHEMOTACTIC PROTEIN 2; MONOCYTE CHEMOTACTIC PROTEIN 3; SHORT HAIRPIN RNA; UNCLASSIFIED DRUG;

ADULT; ANIMAL CELL; ANIMAL CELL CULTURE; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CARDIAC FIBROBLAST; CCN2 GENE; CELL ACTIVATION; CELL ISOLATION; CELL MIGRATION; CHEMOTAXIS; CONTROLLED STUDY; EMBRYO; EXPERIMENTAL MYOCARDIAL INFARCTION; EXTRACELLULAR MATRIX; FIBROBLAST; GENE EXPRESSION; GENE SILENCING; HEART MUSCLE BIOPSY; HEART MUSCLE CELL; HUMAN; HUMAN CELL; HUMAN CELL CULTURE; HUMAN TISSUE; IMMUNOFLUORESCENCE; MALE; MOUSE; NONHUMAN; PLASMID; PRIORITY JOURNAL; PROTEIN ANALYSIS; PROTEIN EXPRESSION; RNA ANALYSIS; RNA INTERFERENCE; SIGNAL TRANSDUCTION;

MURINAE;

ADENOVIRAL VECTOR; ADV; CAR; CCL2; CCL7; CCL8; CCN1; CCN2; CCN3; CCN4; CCN5; CCN6; CHEMOKINE C-C MOTIF LIGAND 2=MCP-1; CONNECTIVE TISSUE GROWTH FACTOR (CTGF); CONNEXIN 43; COXSACKIEVIRUS B3; COXSACKIEVIRUS-ADENOVIRUS-RECEPTOR; CVB3; CX43; CYSTEINE-RICH ANGIOGENIC INDUCER 61 (CYR61); EMB; ENDOMYOCARDIAL BIOPSY; FCS; FETAL CALF SERUM; FIBROSIS; HEART DISEASE; IL10; IMMUNO-THERAPY; INFLAMMATION; INTERLEUKIN 10; LEFT VENTRICULAR EJECTION FRACTION; LEFT VENTRICULAR END-DIASTOLIC DIAMETER; LVEDD; LVEF; MATRIX METALLOPROTEINASE 2; MCP-2; MCP-3; MI; MICRORNA; MIR; MMP2; MOI; MULTIPLICITY OF INFECTION; MYOCARDIAL INFARCTION; NEUROBLASTOMA OVEREXPRESSED (NOV); OPN; OSTEOPONTIN; PCFB; PFU; PLAQUE FORMING UNITS; PRIMARY CARDIAC FIBROBLAST; QRT-PCR; QUANTITATIVE REVERSE TRANSCRIPTION PCR; REMODELING; RNA INTERFERENCE; RNAI; SHORT HAIRPIN RNA; SHRNA; WNT-INDUCIBLE SIGNALING PATHWAY PROTEIN-1 (WISP1); WNT-INDUCIBLE SIGNALING PATHWAY PROTEIN-2 (WISP2); WNT-INDUCIBLE SIGNALING PATHWAY PROTEIN-3 (WISP3);

ADENOVIRIDAE; ANIMALS; CHEMOKINE CCL7; CHEMOKINE CCL8; CONNECTIVE TISSUE GROWTH FACTOR; FIBROBLASTS; FIBROSIS; GENE EXPRESSION REGULATION; GENE SILENCING; GENETIC VECTORS; HUMANS; INFLAMMATION; MATRIX METALLOPROTEINASE 2; MATRIX METALLOPROTEINASE 9; MICE; MOLECULAR TARGETED THERAPY; MYOCARDIUM; MYOCYTES, CARDIAC; PRIMARY CELL CULTURE; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION;

EID: 84890290138     PISSN: 00222828     EISSN: 10958584     Source Type: Journal    
DOI: 10.1016/j.yjmcc.2013.11.004     Document Type: Article

References (66)

1. Hajjar R.J. Potential of gene therapy as a treatment for heart failure. J Clin Invest 2013, 123:53-61.
2. Jessup M., Greenberg B., Mancini D., Cappola T., Pauly D.F., Jaski B., et al. Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID): A phase 2 trial of intracoronary gene therapy of sarcoplasmic reticulum Ca2+-ATPase in patients with advanced heart failure. Circulation 2011, 124:304-313.
3. Suckau L., Fechner H., Chemaly E., Krohn S., Hadri L., Kockskamper J., et al. Long-term cardiac-targeted RNA interference for the treatment of heart failure restores cardiac function and reduces pathological hypertrophy. Circulation 2009, 119:1241-1252.
4. Ottaviano F.G., Yee K.O. Communication signals between cardiac fibroblasts and cardiac myocytes. J Cardiovasc Pharmacol 2011, 57:513-521.
5. Jun J.I., Lau L.F. Taking aim at the extracellular matrix: CCN proteins as emerging therapeutic targets. Nat Rev Drug Discov 2011, 10:945-963.
6. Wittchen F., Suckau L., Witt H., Skurk C., Lassner D., Fechner H., et al. Genomic expression profiling of human inflammatory cardiomyopathy (DCMi) suggests novel therapeutic targets. J Mol Med 2007, 85:257-271.
7. Booth A.J., Bishop D.K. TGF-beta, IL-6, IL-17 and CTGF direct multiple pathologies of chronic cardiac allograft rejection. Immunotherapy 2010, 2:511-520.
8. Azevedo C.F., Nigri M., Higuchi M.L., Pomerantzeff P.M., Spina G.S., Sampaio R.O., et al. Prognostic significance of myocardial fibrosis quantification by histopathology and magnetic resonance imaging in patients with severe aortic valve disease. J Am Coll Cardiol 2012, 56:278-287.
9. Green J.J., Berger J.S., Kramer C.M., Salerno M. Prognostic value of late gadolinium enhancement in clinical outcomes for hypertrophic cardiomyopathy. JACC Cardiovasc Imaging 2012, 5:370-377.
10. Klem I., Weinsaft J.W., Bahnson T.D., Hegland D., Kim H.W., Hayes B., et al. Assessment of myocardial scarring improves risk stratification in patients evaluated for cardiac defibrillator implantation. J Am Coll Cardiol 2012, 60:408-420.
11. Saito M., Okayama H., Yoshii T., Higashi H., Morioka H., Hiasa G., et al. Clinical significance of global two-dimensional strain as a surrogate parameter of myocardial fibrosis and cardiac events in patients with hypertrophic cardiomyopathy. Eur Heart J Cardiovasc Imaging 2012, 13:617-623.
12. Frangogiannis N.G. Matricellular proteins in cardiac adaptation and disease. Physiol Rev 2012, 92:635-688.
13. Duisters R.F., Tijsen A.J., Schroen B., Leenders J.J., Lentink V., van der Made I., et al. miR-133 and miR-30 regulate connective tissue growth factor: implications for a role of microRNAs in myocardial matrix remodeling. Circ Res 2009, 104:170-178.
14. Jiang X., Tsitsiou E., Herrick S.E., Lindsay M.A. MicroRNAs and the regulation of fibrosis. FEBS J 2010, 277:2015-2021.
15. Matkovich S.J., Wang W., Tu Y., Eschenbacher W.H., Dorn L.E., Condorelli G., et al. MicroRNA-133a protects against myocardial fibrosis and modulates electrical repolarization without affecting hypertrophy in pressure-overloaded adult hearts. Circ Res 2010, 106:166-175.
16. Frangogiannis N.G. Regulation of the inflammatory response in cardiac repair. Circ Res 2012, 110:159-173.
17. Chen W., Saxena A., Li N., Sun J., Gupta A., Lee D.W., et al. Endogenous IRAK-M attenuates postinfarction remodeling through effects on macrophages and fibroblasts. Arterioscler Thromb Vasc Biol 2012, 32:2598-2608.
18. Westermann D., Becher P.M., Lindner D., Savvatis K., Xia Y., Frohlich M., et al. Selective PDE5A inhibition with sildenafil rescues left ventricular dysfunction, inflammatory immune response and cardiac remodeling in angiotensin II-induced heart failure in vivo. Basic Res Cardiol 2012, 107:308.
19. Seizer P., Klingel K., Sauter M., Westermann D., Ochmann C., Schonberger T., et al. Cyclophilin A affects inflammation, virus elimination and myocardial fibrosis in coxsackievirus B3-induced myocarditis. J Mol Cell Cardiol 2012, 53:6-14.
20. Westermann D., Lindner D., Kasner M., Zietsch C., Savvatis K., Escher F., et al. Cardiac inflammation contributes to changes in the extracellular matrix in patients with heart failure and normal ejection fraction. Circ Heart Fail 2011, 4:44-52.
21. Westermann D., Savvatis K., Lindner D., Zietsch C., Becher P.M., Hammer E., et al. Reduced degradation of the chemokine MCP-3 by matrix metalloproteinase-2 exacerbates myocardial inflammation in experimental viral cardiomyopathy. Circulation 2011, 124:2082-2093.
22. Dobaczewski M., Bujak M., Li N., Gonzalez-Quesada C., Mendoza L.H., Wang X.F., et al. Smad3 signaling critically regulates fibroblast phenotype and function in healing myocardial infarction. Circ Res 2010, 107:418-428.
23. Jun J.I., Lau L.F. The matricellular protein CCN1 induces fibroblast senescence and restricts fibrosis in cutaneous wound healing. Nat Cell Biol 2010, 12:676-685.
24. Hermida N., Lopez B., Gonzalez A., Dotor J., Lasarte J.J., Sarobe P., et al. A synthetic peptide from transforming growth factor-beta1 type III receptor prevents myocardial fibrosis in spontaneously hypertensive rats. Cardiovasc Res 2009, 81:601-609.
25. Wang X., Wu G., Gou L., Liu Z., Wang X., Fan X., et al. A novel single-chain-Fv antibody against connective tissue growth factor attenuates bleomycin-induced pulmonary fibrosis in mice. Respirology 2011, 16:500-507.
26. Lopez B., Gonzalez A., Beaumont J., Querejeta R., Larman M., Diez J. Identification of a potential cardiac antifibrotic mechanism of torasemide in patients with chronic heart failure. J Am Coll Cardiol 2007, 50:859-867.
27. Antoniu S.A. Pirfenidone for the treatment of idiopathic pulmonary fibrosis. Expert Opin Investig Drugs 2006, 15:823-828.
28. Aoki Y., Maeno T., Aoyagi K., Ueno M., Aoki F., Aoki N., et al. Pioglitazone, a peroxisome proliferator-activated receptor gamma ligand, suppresses bleomycin-induced acute lung injury and fibrosis. Respiration 2009, 77:311-319.
29. Rother M., Krohn S., Kania G., Vanhoutte D., Eisenreich A., Wang X., et al. Matricellular signaling molecule CCN1 attenuates experimental autoimmune myocarditis by acting as a novel immune cell migration modulator. Circulation 2010, 122:2688-2698.
30. Lobel M., Bauer S., Meisel C., Eisenreich A., Kudernatsch R., Tank J., et al. CCN1: a novel inflammation-regulated biphasic immune cell migration modulator. Cell Mol Life Sci 2012, 69:3101-3113.
31. Vallon V., Wyatt A.W., Klingel K., Huang D.Y., Hussain A., Berchtold S., et al. SGK1-dependent cardiac CTGF formation and fibrosis following DOCA treatment. J Mol Med 2006, 84:396-404.
32. Ponticos M. Connective Tissue growth factor (CCN2) in blood vessels. Vascul Pharmacol 2013, 58:189-193.
33. Lang C., Sauter M., Szalay G., Racchi G., Grassi G., Rainaldi G., et al. Connective tissue growth factor: a crucial cytokine-mediating cardiac fibrosis in ongoing enterovirus myocarditis. J Mol Med 2008, 86:49-60.
34. Ponticos M., Holmes A.M., Shi-wen X., Leoni P., Khan K., Rajkumar V.S., et al. Pivotal role of connective tissue growth factor in lung fibrosis: MAPK-dependent transcriptional activation of type I collagen. Arthritis Rheum 2009, 60:2142-2155.
35. Mannon R.B., Fairchild R. Allograft fibrosis-unmasking the players at the dance. Am J Transplant 2010, 10:201-202.
36. Koehncke C., Lisewski U., Schleussner L., Gaertner C., Reichert S., Roepke T.K. Isolation and Kv channel recordings in murine atrial and ventricular cardiomyocytes. J Vis Exp 2013, 73:e50145.
37. Lindner D., Zietsch C., Becher P.M., Schulze K., Schultheiss H.P., Tschope C., et al. Differential expression of matrix metalloproteases in human fibroblasts with different origins. Biochem Res Int 2012, 2012:875742.
38. Fechner H., Suckau L., Kurreck J., Sipo I., Wang X., Pinkert S., et al. Highly efficient and specific modulation of cardiac calcium homeostasis by adenovector-derived short hairpin RNA targeting phospholamban. Gene Ther 2007, 14:211-218.
39. Marienfeld U., Haack A., Thalheimer P., Schneider-Rasp S., Brackmann H.-H., Poller W. "Autoreplication" of the vector genome in recombinant adenoviral vectors with different E1 region deletions and transgenes. Gene Ther 1999, 6:1101-1113.
40. Westermann D., Mersmann J., Melchior A., Freudenberger T., Petrik C., Schaefer L., et al. Biglycan is required for adaptive remodeling after myocardial infarction. Circulation 2008, 117:1269-1276.
41. Noutsias M., Rohde M., Block A., Klippert K., Lettau O., Blunert K., et al. Preamplification techniques for real-time RT-PCR analyses of endomyocardial biopsies. BMC Mol Biol 2008, 9:3.
42. Noutsias M., Rohde M., Goldner K., Block A., Blunert K., Hemaidan L., et al. Expression of functional T-cell markers and T-cell receptor Vbeta repertoire in endomyocardial biopsies from patients presenting with acute myocarditis and dilated cardiomyopathy. Eur J Heart Fail 2011, 13:611-618.
43. Poller W., Tank J., Skurk C., Gast M. Cardiovascular RNA interference therapy: the broadening tool and target spectrum. Circ Res 2013, 113:588-602.
44. Yoon P.O., Lee M.A., Cha H., Jeong M.H., Kim J., Jang S.P., et al. The opposing effects of CCN2 and CCN5 on the development of cardiac hypertrophy and fibrosis. J Mol Cell Cardiol 2010, 49:294-303.
45. Bergelson J., Cunningham J., Droguett G., Kurt-Jones E., Krithivas A., Hong J., et al. Isolation of a common receptor for Coxsackie B viruses and adenoviruses 2 and 5. Science 1997, 275:1320-1323.
46. Hidaka C., Milano E., Leopold P., Bergelson J., Hackett N., Finberg R., et al. CAR-dependent and CAR-independent pathways of adenovirus vector-mediated gene transfer and expression in human fibroblasts. J Clin Invest 1999, 103:579-587.
47. Felkin L.E., Lara-Pezzi E., George R., Yacoub M.H., Birks E.J., Barton P.J. Expression of extracellular matrix genes during myocardial recovery from heart failure after left ventricular assist device support. J Heart Lung Transplant 2009, 28:117-122.
48. Wang Q., Usinger W., Nichols B., Gray J., Xu L., Seeley T.W., et al. Cooperative interaction of CTGF and TGF-beta in animal models of fibrotic disease. Fibrogenesis Tissue Repair 2011, 4:4.
49. Sabbah M., Prunier C., Ferrand N., Megalophonos V., Lambein K., De Wever O., et al. CCN5, a novel transcriptional repressor of the transforming growth factor-β signaling pathway. Mol Cell Biol 2011, 31:1459-1469.
50. Chen C.C., Lau L.F. Functions and mechanisms of action of CCN matricellular proteins. Int J Biochem Cell Biol 2009, 41:771-783.
51. Holbourn K.P., Acharya K.R., Perbal B. The CCN family of proteins: structure-function relationships. Trends Biochem Sci 2008, 33:461-473.
52. Guillon-Munos A., Oikonomopoulou K., Michel N., Smith C.R., Petit-Courty A., Canepa S., et al. Kallikrein-related peptidase 12 hydrolyzes matricellular proteins of the CCN family and modifies interactions of CCN1 and CCN5 with growth factors. J Biol Chem 2011, 286:25505-25518.
53. Wang S., Chong Z.Z., Shang Y.C., Maiese K. WISP1 neuroprotection requires FoxO3a post-translational modulation with autoregulatory control of SIRT1. Curr Neurovasc Res 2013, 10:54-69.
54. Trueblood N.A., Xie Z., Communal C., Sam F., Ngoy S., Liaw L., et al. Exaggerated left ventricular dilation and reduced collagen deposition after myocardial infarction in mice lacking osteopontin. Circ Res 2001, 88:1080-1087.
55. Makkar R.R., Smith R.R., Cheng K., Malliaras K., Thomson L.E., Berman D., et al. Intracoronary cardiosphere-derived cells for heart regeneration after myocardial infarction (CADUCEUS): a prospective, randomised phase 1 trial. Lancet 2012, 379:895-904.
56. Bolli R., Chugh A.R., D'Amario D., Loughran J.H., Stoddard M.F., Ikram S., et al. Cardiac stem cells in patients with ischaemic cardiomyopathy (SCIPIO): initial results of a randomised phase 1 trial. Lancet 2011, 378:1847-1857.
57. Chugh A.R., Beache G.M., Loughran J.H., Mewton N., Elmore J.B., Kajstura J., et al. Administration of cardiac stem cells in patients with ischemic cardiomyopathy: the SCIPIO trial: surgical aspects and interim analysis of myocardial function and viability by magnetic resonance. Circulation 2012, 126:S54-S64.
58. Wahab N.A., Brinkman H., Mason R.M. Uptake and intracellular transport of the connective tissue growth factor: a potential mode of action. Biochem J 2001, 359:89-97.
59. Le Y., Zhou Y., Iribarren P., Wang J. Chemokines and chemokine receptors: their manifold roles in homeostasis and disease. Cell Mol Immunol 2004, 1:95-104.
60. Thiele B.J., Doller A., Kahne T., Pregla R., Hetzer R., Regitz-Zagrosek V. RNA-binding proteins heterogeneous nuclear ribonucleoprotein A1, E1, and K are involved in post-transcriptional control of collagen I and III synthesis. Circ Res 2004, 95:1058-1066.
61. Wang X., McLennan S.V., Allen T.J., Twigg S.M. Regulation of pro-inflammatory and pro-fibrotic factors by CCN2/CTGF in H9c2 cardiomyocytes. J Cell Commun Signal 2010, 4:15-23.
62. Weber K.T. Fibrosis in hypertensive heart disease: focus on cardiac fibroblasts. J Hypertens 2004, 22:47-50.
63. Zhang Y., Kanter E.M., Laing J.G., Aprhys C., Johns D.C., Kardami E., et al. Connexin43 expression levels influence intercellular coupling and cell proliferation of native murine cardiac fibroblasts. Cell Commun Adhes 2008, 15:289-303.
64. Kim K.H., Chen C.C., Monzon R.I., Lau L.F. Matricellular protein CCN1 promotes regression of liver Fibrosis through induction of cellular senescence in hepatic myofibroblasts. Mol Cell Biol 2013, 33:2078-2090.
65. Gravning J., Orn S., Kaasboll O.J., Martinov V.N., Manhenke C., Dickstein K., et al. Myocardial connective tissue growth factor (CCN2/CTGF) attenuates left ventricular remodeling after myocardial infarction. PLoS One 2012, 7:e52120.
66. Wu S., Platteau A., Chen S., McNamara G., Whitsett J., Bancalari E. Conditional overexpression of connective tissue growth factor disrupts postnatal lung development. Am J Respir Cell Mol Biol 2011, 42:552-563.