Iloprost reverses established fibrosis in experimental right ventricular failure

European Respiratory Journal

Volumn 45, Issue 2, 2015, Pages 449-462

  Gomez Arroyo, Jose ^a   Sakagami, Masahiro ^a   Syed, Aamer A ^a   Farkas, Laszlo ^a   Van Tassell, Benjamin ^a   Kraskauskas, Donatas ^a   Mizuno, Shiro ^b   Abbate, Antonio ^a   Bogaard, Harm J ^c   Byron, Peter R ^a   Voelkel, Norbert F ^a  

^a VIRGINIA COMMONWEALTH UNIVERSITY   (United States)

^b KANAZAWA MEDICAL UNIVERSITY   (Japan)

^c VU UNIVERSITY MEDICAL CENTER   (Netherlands)

Author keywords

[No Author keywords available]

Indexed keywords

COLLAGEN; CONNECTIVE TISSUE GROWTH FACTOR; CYCLIC AMP DEPENDENT PROTEIN KINASE; GELATINASE B; ILOPROST; MESSENGER RNA; PROCOLLAGEN; SEMAXANIB; TRANSFORMING GROWTH FACTOR BETA1; INDOLE DERIVATIVE; MMP9 PROTEIN, RAT; PYRROLE DERIVATIVE; VASODILATOR AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; AUTOPHAGY; CARDIOVASCULAR PARAMETERS; CELL ACTIVATION; CELL MIGRATION; COLLAGEN DEGRADATION; CONTROLLED STUDY; DRUG EFFECT; ENZYME ACTIVITY; FIBROBLAST; GENE EXPRESSION; HEART MUSCLE CELL; HEART MUSCLE FIBROSIS; HEART RIGHT VENTRICLE FAILURE; HEART RIGHT VENTRICLE FUNCTION; HEART RIGHT VENTRICLE HYPERTROPHY; HUMAN; HUMAN CELL; HYPOXIA; LUNG ARTERY BANDING; LUNG ARTERY PRESSURE; NONHUMAN; PROTEIN EXPRESSION; PULMONARY ARTERY; PULMONARY ARTERY OCCLUSION; PULMONARY HYPERTENSION; RAT; TREADMILL EXERCISE; TREATMENT DURATION; TRICUSPID ANNULUS PLANE SYSTOLIC EXCURSION; TRICUSPID VALVE; ANIMAL; ANOXIA; CHEMICALLY INDUCED; CYTOLOGY; DRUG EFFECTS; ECHOCARDIOGRAPHY; FIBROSIS; HEART VENTRICLE; HEMODYNAMICS; HYPERTROPHY, RIGHT VENTRICULAR; MALE; METABOLISM; PATHOLOGY; PATHOPHYSIOLOGY; PHASE CONTRAST MICROSCOPY; RANDOMIZATION; SPRAGUE DAWLEY RAT;

ANIMALS; ANOXIA; COLLAGEN; CYCLIC AMP-DEPENDENT PROTEIN KINASES; ECHOCARDIOGRAPHY; FIBROBLASTS; FIBROSIS; HEART VENTRICLES; HEMODYNAMICS; HYPERTENSION, PULMONARY; HYPERTROPHY, RIGHT VENTRICULAR; ILOPROST; INDOLES; MALE; MATRIX METALLOPROTEINASE 9; MICROSCOPY, PHASE-CONTRAST; PHYSICAL CONDITIONING, ANIMAL; PROCOLLAGEN; PYRROLES; RANDOM ALLOCATION; RATS; RATS, SPRAGUE-DAWLEY; RNA, MESSENGER; TRANSFORMING GROWTH FACTOR BETA1; VASODILATOR AGENTS; VENTRICULAR FUNCTION, RIGHT;

EID: 84961291825     PISSN: 09031936     EISSN: 13993003     Source Type: Journal    
DOI: 10.1183/09031936.00188013     Document Type: Article

References (52)

1. Benza RL, Miller DP, Gomberg-Maitland M, et al. Predicting survival in pulmonary arterial hypertension: insights from the Registry to Evaluate Early and Long-Term Pulmonary Arterial Hypertension Disease Management (REVEAL). Circulation 2010;122:164-172.
2. Voelkel NF, Gomez-Arroyo J, Abbate A, et al. Pathobiology of pulmonary arterial hypertension and right ventricular failure. Eur Respir J 2012;40:1555-1565.
3. Delcroix M, Spaas K, Quarck R. Long-term outcome in pulmonary arterial hypertension: a plea for earlier parenteral prostacyclin therapy. Eur Respir Rev 2009;18:253-259.
4. van de Veerdonk MC, Kind T, Marcus JT, et al. Progressive right ventricular dysfunction in patients with pulmonary arterial hypertension responding to therapy. J Am Coll Cardiol 2011;58:2511-2519.
5. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004;351:1425-1436.
6. Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 2000;342:1866-1870.
7. Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. N Engl J Med 1996;334:296-302.
8. Olschewski H, Simonneau G, Galiè N, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002;347:322-329.
9. Olschewski H, Hoeper MM, Behr J, et al. Long-term therapy with inhaled iloprost in patients with pulmonary hypertension. Respir Med 2010;104:731-740.
10. McLaughlin VV, Archer SL, Badesch DB, et al. ACCF/AHA 2009 expert consensus document on pulmonary hypertension a report of the American College of Cardiology Foundation Task Force on Expert Consensus Documents and the American Heart Association developed in collaboration with the American College of Chest Physicians; American Thoracic Society, Inc.; and the Pulmonary Hypertension Association. J Am Coll Cardiol 2009;53:1573-1619.
11. Clapp LH, Finney P, Turcato S, et al. Differential effects of stable prostacyclin analogs on smooth muscle proliferation and cyclic AMP generation in human pulmonary artery. Am J Respir Cell Mol Biol 2002;26:194-201.
12. Galiè N, Manes A, Negro L, et al. A meta-analysis of randomized controlled trials in pulmonary arterial hypertension. Eur Heart J 2009;30:394-403.
13. Stacher E, Graham BB, Hunt JM, et al. Modern age pathology of pulmonary arterial hypertension. Am J Respir Crit Care Med 2012;186:261-272.
14. Pogoriler JE, Rich S, Archer SL, et al. Persistence of complex vascular lesions despite prolonged prostacyclin therapy of pulmonary arterial hypertension. Histopathology 2012;61:597-609.
15. Syed A, Gomez-Arroyo J, Sakagami M, et al. Inhaled iloprost improves right ventricular function in the Sugen5416/hypoxia model of severe pulmonary hypertension. Am J Respir Crit Care Med 2012;185:A3415.
16. Bogaard HJ, Natarajan R, Henderson SC, et al. Chronic pulmonary artery pressure elevation is insufficient to explain right heart failure. Circulation 2009;120:1951-1960.
17. Sakao S, Taraseviciene-Stewart L, Cool CD, et al. VEGF-R blockade causes endothelial cell apoptosis, expansion of surviving CD34+ precursor cells and transdifferentiation to smooth muscle-like and neuronal-like cells. FASEB J 2007;21:3640-3652.
18. Gomez-Arroyo J, Mizuno S, Szczepanek K, et al. Metabolic gene remodeling and mitochondrial dysfunction in failing right ventricular hypertrophy secondary to pulmonary arterial hypertension. Circ Heart Fail 2013;6:136-144.
19. Urboniene D, Haber I, Fang YH, et al. Validation of high-resolution echocardiography and magnetic resonance imaging vs. high-fidelity catheterization in experimental pulmonary hypertension. Am J Physiol Lung Cell Mol Physiol 2010;299:L401-L412.
20. Bogaard HJ, Mizuno S, Al-Hussaini AA, et al. Suppression of histone deacetylases worsens right ventricular dysfunction after pulmonary artery banding in rats. Am J Respir Crit Care Med 2011;183:1402-1410.
21. Bogaard HJ, Natarajan R, Mizuno S, et al. Adrenergic receptor blockade reverses right heart remodeling and dysfunction in pulmonary hypertensive rats. Am J Respir Crit Care Med 2010;182:652-660.
22. Gomez-Arroyo J, Saleem SJ, Mizuno S, et al. A brief overview of mouse models of pulmonary arterial hypertension: problems and prospects. Am J Physiol Lung Cell Mol Physiol 2012;302:L977-L991.
23. Stratton R, Rajkumar V, Ponticos M, et al. Prostacyclin derivatives prevent the fibrotic response to TGF-β by inhibiting the Ras/MEK/ERK pathway. FASEB J 2002;16:1949-1951.
24. Oka M, Homma N, Taraseviciene-Stewart L, et al. Rho kinase-mediated vasoconstriction is important in severe occlusive pulmonary arterial hypertension in rats. Circ Res 2007;100:923-929.
25. Abe K, Toba M, Alzoubi A, et al. Formation of plexiform lesions in experimental severe pulmonary arterial hypertension. Circulation 2010;121:2747-2754.
26. Höper MM, Voelkel NF, Bates TO, et al. Prostaglandins induce vascular endothelial growth factor in a human monocytic cell line and rat lungs via cAMP. Am J Respir Cell Mol Biol 1997;17:748-756.
27. Voelkel NF, Hoeper M, Maloney J, et al. Vascular endothelial growth factor in pulmonary hypertension. Ann NY Acad Sci 1996;796:186-193.
28. Drake JI, Bogaard HJ, Mizuno S, et al. Molecular signature of a right heart failure program in chronic severe pulmonary hypertension. Am J Respir Cell Mol Biol 2011;45:1239-1247.
29. Leask A, Abraham DJ. The role of connective tissue growth factor, a multifunctional matricellular protein, in fibroblast biology. Biochem Cell Biol 2003;81:355-363.
30. Shi-Wen X, Pennington D, Holmes A, et al. Autocrine overexpression of CTGF maintains fibrosis: RDA analysis of fibrosis genes in systemic sclerosis. Exp Cell Res 2000;259:213-224.
31. Stratton R, Shiwen X, Martini G, et al. Iloprost suppresses connective tissue growth factor production in fibroblasts and in the skin of scleroderma patients. J Clin Invest 2001;108:241-250.
32. Eghbali M. Cardiac fibroblasts: function, regulation of gene expression, and phenotypic modulation. Basic Res Cardiol 1992;87:Suppl. 2, 183-189.
33. Creemers EE, Pinto YM. Molecular mechanisms that control interstitial fibrosis in the pressure-overloaded heart. Cardiovasc Res 2011;89:265-272.
34. Tomasek JJ, Gabbiani G, Hinz B, et al. Myofibroblasts and mechano-regulation of connective tissue remodelling. Nat Rev Mol Cell Biol 2002;3:349-363.
35. Arndt S, Schmidt J, Wacker E, et al. Fussel-15, a new player in wound healing, is deregulated in keloid and localized scleroderma. Am J Pathol 2011;178:2622-2631.
36. Spinale FG. Myocardial matrix remodeling and the matrix metalloproteinases: influence on cardiac form and function. Physiol Rev 2007;87:1285-1342.
37. Aránguiz-Urroz P, Canales J, Copaja M, et al. β2-adrenergic receptor regulates cardiac fibroblast autophagy and collagen degradation. Biochim Biophys Acta 2011;1812:23-31.
38. Kim SI, Na HJ, Ding Y, et al. Autophagy promotes intracellular degradation of type I collagen induced by transforming growth factor (TGF)-β1. J Biol Chem 2012;287:11677-11688.
39. Maiuri MC, Zalckvar E, Kimchi A, et al. Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 2007;8:741-752.
40. Voelkel NF, Gerber JG, McMurtry IF, et al. Release of vasodilator prostaglandin, PGI2, from isolated rat lung during vasoconstriction. Circ Res 1981;48:207-213.
41. Falcetti E, Hall SM, Phillips PG, et al. Smooth muscle proliferation and role of the prostacyclin (IP) receptor in idiopathic pulmonary arterial hypertension. Am J Respir Crit Care Med 2010;182:1161-1170.
42. Lai YJ, Pullamsetti SS, Dony E, et al. Role of the prostanoid EP4 receptor in iloprost-mediated vasodilatation in pulmonary hypertension. Am J Respir Crit Care Med 2008;178:188-196.
43. Ogo T, Chowdhury HM, Yang J, et al. Inhibition of overactive transforming growth factor-β signaling by prostacyclin analogues in pulmonary arterial hypertension. Am J Respir Cell Mol Biol 2013;48:733-741.
44. Pullamsetti SS, Doebele C, Fischer A, et al. Inhibition of microRNA-17 improves lung and heart function in experimental pulmonary hypertension. Am J Respir Crit Care Med 2012;185:409-419.
45. Rich S, Pogoriler J, Husain AN, et al. Long-term effects of epoprostenol on the pulmonary vasculature in idiopathic pulmonary arterial hypertension. Chest 2010;138:1234-1239.
46. Francois H, Athirakul K, Howell D, et al. Prostacyclin protects against elevated blood pressure and cardiac fibrosis. Cell Metab 2005;2:201-207.
47. Hara A, Yuhki KI, Fujino T, et al. Augmented cardiac hypertrophy in response to pressure overload in mice lacking the prostaglandin I2 receptor. Circulation 2005;112:84-92.
48. Leask A, Holmes A, Black CM, et al. Connective tissue growth factor gene regulation. Requirements for its induction by transforming growth factor-beta 2 in fibroblasts. J Biol Chem 2003;278:13008-13015.
49. Chen MM, Lam A, Abraham JA, et al. CTGF expression is induced by TGF-beta in cardiac fibroblasts and cardiac myocytes: a potential role in heart fibrosis. J Mol Cell Cardiol 2000;32:1805-1819.
50. Rain S, Handoko ML, Trip P, et al. Right ventricular diastolic impairment in patients with pulmonary arterial hypertension. Circulation 2013;128:2016-2025.
51. Rex S, Missant C, Claus P, et al. Effects of inhaled iloprost on right ventricular contractility, right ventriculo-vascular coupling and ventricular interdependence: a randomized placebo-controlled trial in an experimental model of acute pulmonary hypertension. Crit Care 2008;12:R113.
52. Fontana M, Olschewski H, Olschewski A, et al. Treprostinil potentiates the positive inotropic effect of catecholamines in adult rat ventricular cardiomyocytes. Br J Pharmacol 2007;151:779-786.