Combined NOX1/4 inhibition with GKT137831 in mice provides dose-dependent reno- and atheroprotection even in established micro- and macrovascular disease

Diabetologia

Volumn 60, Issue 5, 2017, Pages 927-937

  Gray, Stephen P ^a,b   Jha, Jay C ^a   Kennedy, Kit ^a   van Bommel, Erik ^a   Chew, Phyllis ^a   Szyndralewiez, Cedric ^c   Touyz, Rhian M ^d   Schmidt, Harald H H W ^e,f   Cooper, Mark E ^a,b   Jandeleit Dahm, Karin A M ^a,b  

^a BAKER IDI HEART AND DIABETES INSTITUTE   (Australia)

^b MONASH UNIVERSITY   (Australia)

^c GENKYOTEX SA   (Switzerland)

^d UNIVERSITY OF GLASGOW   (United Kingdom)

^e MAASTRICHT UNIVERSITY   (Netherlands)

^f MAASTRICHT UNIVERSITY   (Netherlands)

Author keywords

Atherosclerosis; Diabetes; NADPH oxidase; Nephropathy; Oxidative stress

Indexed keywords

2 (2 CHLOROPHENYL) 4 [3 (DIMETHYLAMINO)PHENYL] 5 METHYL 1H PYRAZOLO[4,3 C]PYRIDINE 3,6(2H,5H) DIONE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 1; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; NOX4 PROTEIN, MOUSE; OXIDOREDUCTASE; PYRAZOLE DERIVATIVE; PYRIDINE DERIVATIVE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; ATHEROPROTECTION; ATHEROSCLEROTIC PLAQUE; CONTROLLED STUDY; DIABETIC NEPHROPATHY; DIABETOGENESIS; DISEASE COURSE; ENZYME INHIBITION; MACROVASCULAR DISEASE; MALE; MICROANGIOPATHY; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTECTION; RENAL PROTECTION; STREPTOZOTOCIN-INDUCED DIABETES MELLITUS; VASCULAR DISEASE; ANIMAL; ANTAGONISTS AND INHIBITORS; ATHEROSCLEROSIS; DEFICIENCY; DIABETES COMPLICATIONS; DIABETES MELLITUS, EXPERIMENTAL; DIABETIC NEPHROPATHIES; DRUG EFFECTS; GENETICS; KNOCKOUT MOUSE; METABOLISM; OXIDATIVE STRESS;

ANIMALS; ATHEROSCLEROSIS; DIABETES COMPLICATIONS; DIABETES MELLITUS, EXPERIMENTAL; DIABETIC NEPHROPATHIES; MICE; MICE, KNOCKOUT; NADH, NADPH OXIDOREDUCTASES; NADPH OXIDASE; OXIDATIVE STRESS; PYRAZOLES; PYRIDINES;

EID: 85011551497     PISSN: 0012186X     EISSN: 14320428     Source Type: Journal    
DOI: 10.1007/s00125-017-4215-5     Document Type: Article

References (37)

1. Shaw JE, Sicree RA, Zimmet PZ (2010) Global estimates of the prevalence of diabetes for 2010 and 2030. Diabetes Res Clin Pract 87:4–14
2. Bedard K, Krause KH (2007) The NOX family of ROS-generating NADPH oxidases: physiology and pathophysiology. Physiol Rev 87:245–313
3. Brandes RP, Weissmann N, Schroder K (2010) NADPH oxidases in cardiovascular disease. Free Radic Biol Med 49:687–706
4. Lassegue B, Griendling KK (2010) NADPH oxidases: functions and pathologies in the vasculature. Arterioscler Thromb Vasc Biol 30:653–661
5. Gray SP, Di Marco E, Okabe J et al (2013) NADPH oxidase 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation 127:1888–1902
6. Jha JC, Gray SP, Barit D et al (2014) Genetic targeting or pharmacologic inhibition of NADPH oxidase nox4 provides renoprotection in long-term diabetic nephropathy. J Am Soc Nephrol 25:1237–1254
7. Stolk J, Hiltermann TJ, Dijkman JH, Verhoeven AJ (1994) Characteristics of the inhibition of NADPH oxidase activation in neutrophils by apocynin, a methoxy-substituted catechol. Am J Respir Cell Mol Biol 11:95–102
8. Ferreira Mendes A, Pato Carvalho A, Margarida Caramona M, Celeste Lopes M (2001) Diphenyleneiodonium inhibits NF-κB activation and iNOS expression induced by IL-1β: involvement of reactive oxygen species. Mediat Inflamm 10:209–215
9. Heumuller S, Wind S, Barbosa-Sicard E et al (2008) Apocynin is not an inhibitor of vascular NADPH oxidases but an antioxidant. Hypertension 51:211–217
10. Riganti C, Gazzano E, Polimeni M, Costamagna C, Bosia A, Ghigo D (2004) Diphenyleneiodonium inhibits the cell redox metabolism and induces oxidative stress. J Biol Chem 279:47726–47731
11. Casas AI, Dao VT, Daiber A et al (2015) Reactive oxygen-related diseases: therapeutic targets and emerging clinical indications. Antioxid Redox Signal 23:1171–1185
12. −/− mice. Diabetologia 57:633–642
13. Gavazzi G, Banfi B, Deffert C et al (2006) Decreased blood pressure in NOX1-deficient mice. FEBS Lett 580:497–504
14. Kleinschnitz C, Grund H, Wingler K, et al. (2010) Post-stroke inhibition of induced NADPH oxidase type 4 prevents oxidative stress and neurodegeneration. PLoS Biol 8:e1000479
15. Krege JH, Hodgin JB, Hagaman JR, Smithies O (1995) A noninvasive computerized tail-cuff system for measuring blood pressure in mice. Hypertension 25:1111–1115
16. Jiang JX, Chen X, Serizawa N et al (2012) Liver fibrosis and hepatocyte apoptosis are attenuated by GKT137831, a novel NOX4/NOX1 inhibitor in vivo. Free Radic Biol Med 53:289–296
17. Aoyama T, Paik YH, Watanabe S et al (2012) Nicotinamide adenine dinucleotide phosphate oxidase in experimental liver fibrosis: GKT137831 as a novel potential therapeutic agent. Hepatology 56:2316–2327
18. Candido R, Allen TJ, Lassila M et al (2004) Irbesartan but not amlodipine suppresses diabetes-associated atherosclerosis. Circulation 109:1536–1542
19. Watson AM, Li J, Schumacher C et al (2010) The endothelin receptor antagonist avosentan ameliorates nephropathy and atherosclerosis in diabetic apolipoprotein E knockout mice. Diabetologia 53:192–203
20. Watson AM, Gray SP, Jiaze L et al (2012) Alagebrium reduces glomerular fibrogenesis and inflammation beyond preventing RAGE activation in diabetic apolipoprotein E knockout mice. Diabetes 61:2105–2113
21. Chew P, Yuen DY, Stefanovic N et al (2010) Antiatherosclerotic and renoprotective effects of ebselen in the diabetic apolipoprotein E/GPx1-double knockout mouse. Diabetes 59:3198–3207
22. Tikellis C, Bialkowski K, Pete J et al (2008) ACE2 deficiency modifies renoprotection afforded by ACE inhibition in experimental diabetes. Diabetes 57:1018–1025
23. Wang B, Jha JC, Hagiwara S et al (2014) Transforming growth factor-β1-mediated renal fibrosis is dependent on the regulation of transforming growth factor receptor 1 expression by let-7b. Kidney Int 85:352–361
24. Coughlan MT, Thallas-Bonke V, Pete J et al (2007) Combination therapy with the advanced glycation end product cross-link breaker, alagebrium, and angiotensin converting enzyme inhibitors in diabetes: synergy or redundancy? Endocrinology 148:886–895
25. Watson AM, Li J, Samijono D et al (2014) Quinapril treatment abolishes diabetes-associated atherosclerosis in RAGE/apolipoprotein E double knockout mice. Atherosclerosis 235:444–448
26. Candido R, Jandeleit-Dahm KA, Cao Z et al (2002) Prevention of accelerated atherosclerosis by angiotensin-converting enzyme inhibition in diabetic apolipoprotein E-deficient mice. Circulation 106:246–253
27. Watson AM, Olukman M, Koulis C et al (2013) Urotensin II receptor antagonism confers vasoprotective effects in diabetes associated atherosclerosis: studies in humans and in a mouse model of diabetes. Diabetologia 56:1155–1165
28. Gray SP, Di Marco E, Kennedy K et al (2016) Reactive oxygen species can provide atheroprotection via nox4-dependent inhibition of inflammation and vascular remodeling. Arterioscler Thromb Vasc Biol 36:295–307
29. Jha JC, Thallas-Bonke V, Banal C et al (2016) Podocyte-specific Nox4 deletion affords renoprotection in a mouse model of diabetic nephropathy. Diabetologia 59:379–389
30. You YH, Quach T, Saito R, Pham J, Sharma K (2016) Metabolomics reveals a key role for fumarate in mediating the effects of NADPH oxidase 4 in diabetic kidney disease. J Am Soc Nephrol 27:466–481
31. Gorin Y, Cavaglieri RC, Khazim K et al (2015) Targeting NADPH oxidase with a novel dual Nox1/Nox4 inhibitor attenuates renal pathology in type 1 diabetes. Am J Physiol Renal Physiol 308:F1276–F1287
32. Wilkinson-Berka JL, Deliyanti D, Rana I et al (2014) NADPH oxidase, NOX1, mediates vascular injury in ischemic retinopathy. Antioxid Redox Signal 20:2726–2740
33. Coughlan MT, Thorburn DR, Penfold SA et al (2009) RAGE-induced cytosolic ROS promote mitochondrial superoxide generation in diabetes. J Am Soc Nephrol 20:742–752
34. Kuroda J, Ago T, Nishimura A et al (2014) Nox4 is a major source of superoxide production in human brain pericytes. J Vasc Res 51:429–438
35. Zheleznova N, O’Connor P, Cowley A (2015) Role of NOX4 in superoxide production stimulated by H+ efflux in mTAL of SS rat. The FASEB Journal 29:S963.10
36. Lu Q, Zhai Y, Cheng Q et al (2013) The Akt-FoxO3a-manganese superoxide dismutase pathway is involved in the regulation of oxidative stress in diabetic nephropathy. Exp Physiol 98:934–945
37. Genkyotex (2015) Genkyotex announces top-line results of phase 2 clinical program. Available from www.genkyotex.com/genkyotex/index.cfm/news-events/genkyotex-announces-top-line-results-of-phase-2-clinical-program/. Accessed 1 Sept 2015