Vascular injury in diabetic db/db mice is ameliorated by atorvastatin: Role of Rac1/2-sensitive Nox-dependent pathways

Clinical Science

Volumn 128, Issue 7, 2015, Pages 411-423

  Bruder Nascimento, Thiago ^a,b   Callera, Glaucia E ^b   Montezano, Augusto C ^c   He, Ying ^b   Antunes, Tayze T ^b   Dinh Cat, Aurelie Nguyen ^c   Tostes, Rita C ^a   Touyz, Rhian M ^a,c  

^a UNIVERSITY OF SÃO PAULO   (Brazil)

^b OTTAWA HOSPITAL RESEARCH INSTITUTE   (Canada)

^c UNIVERSITY OF GLASGOW   (United Kingdom)

Author keywords

Inflammation; NADPH oxidase (Nox); Oxidative stress; Statin; Type 2 diabetes; Vascular function

Indexed keywords

ACETYLCHOLINE; ATORVASTATIN; GUANOSINE TRIPHOSPHATASE; I KAPPA B ALPHA; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; INSULIN; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN P47 PHOX; RAC1 PROTEIN; RAC2 PROTEIN; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; THIOBARBITURIC ACID REACTIVE SUBSTANCE; TRANSCRIPTION FACTOR RELA; UNCLASSIFIED DRUG; VASCULAR CELL ADHESION MOLECULE 1; ANTIDIABETIC AGENT; HEPTANOIC ACID DERIVATIVE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE INHIBITOR; LEPTIN RECEPTOR; LIPID; NEUTROPHIL CYTOSOLIC FACTOR 1; PYRROLE DERIVATIVE; RAC PROTEIN; VASODILATOR AGENT;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BLOOD LEVEL; BLOOD VESSEL INJURY; CELL ADHESION; CELL MEMBRANE; CONTROLLED STUDY; CYTOSOL; DRUG EFFECT; DRUG MECHANISM; ENZYME ACTIVITY; GLUCOSE TOLERANCE; MONOCYTE; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE STRESS; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN TRANSPORT; SIGNAL TRANSDUCTION; VASCULITIS; VASODILATATION; ANIMAL; ARTERY; BLOOD; DRUG EFFECTS; GENETICS; IN VITRO STUDY; MALE; METABOLISM; MUTANT MOUSE STRAIN; PATHOPHYSIOLOGY; PHOSPHORYLATION; PHYSIOLOGY; WESTERN BLOTTING;

ACETYLCHOLINE; ANIMALS; ARTERIES; ATORVASTATIN CALCIUM; BLOTTING, WESTERN; DIABETES MELLITUS, TYPE 2; HEPTANOIC ACIDS; HYDROXYMETHYLGLUTARYL-COA REDUCTASE INHIBITORS; HYPOGLYCEMIC AGENTS; IN VITRO TECHNIQUES; INSULIN; LIPIDS; MALE; MICE, MUTANT STRAINS; MITOGEN-ACTIVATED PROTEIN KINASES; NADPH OXIDASE; PHOSPHORYLATION; PYRROLES; RAC GTP-BINDING PROTEINS; RAC1 GTP-BINDING PROTEIN; REACTIVE OXYGEN SPECIES; RECEPTORS, LEPTIN; SIGNAL TRANSDUCTION; THIOBARBITURIC ACID REACTIVE SUBSTANCES; VASODILATION; VASODILATOR AGENTS;

EID: 84941622608     PISSN: 01435221     EISSN: 14708736     Source Type: Journal    
DOI: 10.1042/CS20140456     Document Type: Article

References (59)

1. Zhou, Q. and Liao, J. K. (2009) Statins and cardiovascular diseases: from cholesterol lowering to pleiotropy. Curr. Pharm. Des. 15, 467-478
2. Rashid, M., Tawara, S., Fukumoto, Y., Seto, M., Yano, K. and Shimokawa, H. (2009) Importance of Rac1 signaling pathway inhibition in the pleiotropic effects of HMG-CoA reductase inhibitors. Circ. J. 73, 361-370
3. Takemoto, M., Node, K, Nakagami, H., Liao, Y., Grimm, M., Takemoto, Y., Kitakaze, M. and Liao, J. K. (2001) Statins as antioxidant therapy for preventing cardiac myocyte hypertrophy. J. Clin. Invest. 108, 1429-1437
4. Kwok, J. M., Ma, C. C. and Ma, S. (2013) Recent development in the effects of statins on cardiovascular disease through Rac1 and NADPH oxidase. Vascul. Pharmacol. 58, 21-30
5. Antonopoulos, A. S., Margaritis, M., Shirodaria, C. and Antoniades, C. (2012) Translating the effects of statins: from redox regulation to suppression of vascular wall inflammation. Thromb. Haemost. 108, 840-848
6. Margaritis, M., Channon, K. M. and Antoniades, C. (2014) Statins as regulators of redox state in the vascular endothelium: beyond lipid lowering. Antioxid. Redox Signal. 20, 1198-1215
7. Hermida, N. and Balligand, J. L. (2014) Low-density lipoprotein-cholesterol-induced endothelial dysfunction and oxidative stress: the role of statins. Antioxid. Redox Signal. 20, 1216-1237
8. Wang, L., Shi, J. and Zhang, Y. (2013) Influences of simvastatin on vascular endothelial function of patients with coronary heart disease complicated with congestive heart failure. Eur. Rev. Med. Pharmacol. Sci. 17, 1590-1593
9. Kang, S., Woo, H. H., Kim, K., Lim, K. M., Noh, J. Y., Lee, M. Y., Bae, Y. M., Bae, O. N. and Chung, J. H. (2014) Dysfunction of vascular smooth muscle and vascular remodeling by simvastatin. Toxicol. Sci. 138, 446-556
10. Tousoulis, D., Papageorgiou, N., Androulakis, E., Siasos, G., Latsios, G., Tentolouris, K. and Stefanadis, C. (2013) Diabetes mellitus-associated vascular impairment: novel circulating biomarkers and therapeutic approaches. J. Am. Coll Cardiol. 62, 667-676
11. Lee, H. Y., Youn, S. W., Cho, H. J., Kwon, Y. W., Lee, S. W., Kim, S. J., Park, Y. B., Oh, B. H. and Kim, H. S. (2013) FOXO1 impairs whereas statin protects endothelial function in diabetes through reciprocal regulation of Kruppel-like factor 2. Cardiovasc Res. 97, 143-152
12. Tian, X. Y., Wong, W. T., Xu, A., Chen, Z. Y., Lu, Y., Liu, L. M., Lee, V. W., Lau, C. W., Yao, X. and Huang, Y. (2011) Rosuvastatin improves endothelial function in db/db mice: role of angiotensin II type 1 receptors and oxidative stress. Br. J. Pharmacol. 164, 598-606
13. Ishibashi, Y., Matsui, T., Takeuchi, M. and Yamagishi, S. (2011) Rosuvastatin blocks advanced glycation end products elicited reduction of macrophage cholesterol efflux by suppressing NADPH oxidase activity via inhibition of geranylgeranylation of Rac-1. Horm. Metab. Res. 43, 619-624
14. Briones, A. M., Rodríguez-Criado, N., Hernanz, R., García-Redondo, A. B., Rodrigues-Díez, R. R., Alonso, M. J., Egido, J., Ruiz-Ortega, M. and Salaices, M. (2009) Atorvastatin prevents angiotensin II-induced vascular remodeling and oxidative stress. Hypertension 54, 142-249
15. Xiao, H., Qin, X., Ping, D. and Zuo, K. (2013) Inhibition of Rho and Rac geranylgeranylation by atorvastatin is critical for preservation of endothelial junction integrity. PLoS ONE 8, e59233
16. Cheng, W. H., Ho, W. Y., Chang, C. F., Lu, P. J., Cheng, P. W., Yeh, T. C., Hong, L. Z., Sun, G. C., Hsiao, M. and Tseng, C. J. (2013) Simvastatin induces a central hypotensive effect via Ras-mediated signalling to cause eNOS up-regulation. Br. J. Pharmacol. 170, 847-858
17. Pignatelli, P., Carnevale, R., Pastori, D., Cangemi, R., Napoleone, L., Bartimoccia, S., Nocella, C., Basili, S. and Violi, F. (2012) Immediate antioxidant and antiplatelet effect of atorvastatin via inhibition of Nox2. Circulation 126, 92-103
18. Cui, W., Matsuno, K., Iwata, K., Ibi, M, Katsuyama, M., Kakehi, T., Sasaki, M., Ikami, K., Zhu, K. and Yabe-Nishimura, C. (2009) NADPH oxidase isoforms and anti-hypertensive effects of atorvastatin demonstrated in two animal models. J. Pharmacol. Sci. 111, 260-268
19. Nguyen Dinh Cat, A., Montezano, A. C., Burger, D. and Touyz, R. M. (2013) Angiotensin II, NADPH oxidase, and redox signaling in the vasculature. Antioxid. Redox Signal. 19, 1110-1120
20. Paravicini, T. M. and Touyz, R. M. (2008) NADPH oxidases, reactive oxygen species, and hypertension: clinical implications and therapeutic possibilities. Diabetes Care. 31 (Suppl. 2), S170-S180
21. Pick, E. (2014) Role of the Rho GTPase Rac in the activation of the phagocyte NADPH oxidase: outsourcing a key task. Small GTPases. 5, e27952
22. Kowluru, R. A., Kowluru, A., Veluthakal, R., Mohammad, G., Syed, I., Santos, J. M. and Mishra, M. (2014) TIAM1-RAC1 signalling axis-mediated activation of NADPH oxidase-2 initiates mitochondrial damage in the development of diabetic retinopathy. Diabetologia 57, 1047-1056
23. Schalkwijk, C. G. and Stehouwer, C. D. (2005) Vascular complications in diabetes mellitus: the role of endothelial dysfunction. Clin. Sci. 109, 143-159
24. Di Marco, E., Gray, S. P., Chew, P., Koulis, C., Ziegler, A., Szyndralewiez, C., Touyz, R. M, Schmidt, H. H., Cooper, M. E., Slattery, R. and Jandeleit-Dahm, K. A. (2014) Pharmacological inhibition of NOX reduces atherosclerotic lesions, vascular ROS and immune-inflammatory responses in diabetic Apoe(-/-) mice. Diabetologia 57, 633-642
25. Holterman, C. E., Thibodeau, J. F., Towaij, C., Gutsol, A., Montezano, A. C., Parks, R. J., Cooper, M. E., Touyz, R. M. and Kennedy, C. R. (2014) Nephropathy and elevated BP in mice with podocyte-specific NADPH oxidase 5 expression. J. Am. Soc. Nephrol. 25, 784-797
26. Gray, S. P., Di Marco, E., Okabe, J., Szyndralewiez, C., Heitz, F., Montezano, A. C., de Haan, J. B., Koulis, C., El-Osta, A., Andrews, K. L., Chin-Dusting, J. P., Touyz, R. M., Wingler, K., Cooper, M. E., Schmidt, H. H. and Jandeleit-Dahm, K. A. (2013) NADPH oxidase. 1 plays a key role in diabetes mellitus-accelerated atherosclerosis. Circulation 127, 1888-1902
27. Koladiya, R. U., Jaggi, A. S., Singh, N. and Sharma, B. K. (2008) Ameliorative role of atorvastatin and pitavastatin in L-methionine induced vascular dementia in rats. BMC Pharmacol. 8, 14
28. Nie, P., Li, D., Hu, L., Jin, S., Yu, Y., Cai, Z., Shao, Q., Shen, J., Yi, J., Xiao, H. et al. (2014) Atorvastatin improves plaque stability in ApoE-knockout mice by regulating chemokines and chemokine receptors. PLoS ONE 9, e97009
29. Briones, A. M., Nguyen Dinh Cat, A., Callera, G. E., Yogi, A., Burger, D., He, Y., Corrêa, J. W., Gagnon, A. M., Gomez-Sanchez, C. E., Gomez-Sanchez, E. P. et al. (2012) Adipocytes produce aldosterone through calcineurin-dependent signaling pathways: implications in diabetes mellitus-associated obesity and vascular dysfunction. Hypertension 59, 1069-1078
30. Callera, G. E., Tostes, R. C., Yogi, A., Montezano, A. C. and Touyz, R. M. (2006) Endothelin-1-induced oxidative stress in DOCA-salt hypertension involves NADPH-oxidase-independent mechanisms. Clin. Sci. 110, 243-253
31. The Global Burden of Metabolic Risk Factors for Chronic Diseases Collaboration (2014) Cardiovascular disease, chronic kidney disease, and diabetes mortality burden of cardiometabolic risk factors from 1980 to 2010: a comparative risk assessment. Lancet Diabetes Endocrinol. 2, 634-647
32. Uğurlu, N., Gerceker, S., Yülek, F., Ugurlu, B., Sari, C., Baran, P. and Çağil, N. (2013) The levels of the circulating cellular adhesion molecules ICAM-1, VCAM-1 and endothelin-1 and the flow-mediated vasodilatation values in patients with type 1 diabetes mellitus with early-stage diabetic retinopathy. Intern. Med. 52, 2173-2178
33. Naka, K. K., Papathanassiou, K., Bechlioulis, A., Kazakos, N., Pappas, K., Tigas, S., Makriyiannis, D., Tsatsoulis, A. and Michalis, L. K. (2012) Determinants of vascular function in patients with type 2 diabetes. Cardiovasc. Diabetol. 11, 127-130
34. Chen, B., Zhao, Q., Ni, R., Tang, F., Shan, L., Cepinskas, I., Cepinskas, G., Wang, W., Schiller, P. W. and Peng, T. (2014) Inhibition of calpain reduces oxidative stress and attenuates endothelial dysfunction in diabetes. Cardiovasc. Diabetol. 13, 88
35. Wenzel, P., Daiber, A., Oelze, M., Brandt, M., Closs, E., Xu, J., Thum, T., Bauersachs, J., Ertl, G., Zou, M. H., Förstermann, U. and Münzel, T. (2008) Mechanisms underlying recoupling of eNOS by HMG-CoA reductase inhibition in a rat model of streptozotocin-induced diabetes mellitus. Atherosclerosis 198, 65-76
36. Lau, Y. S., Tian, X. Y., Mustafa, M. R., Murugan, D., Liu, J., Zhang, Y., Lau, C. W. and Huang, Y. (2013) Boldine improves endothelial function in diabetic db/db mice through inhibition of angiotensin II-mediated BMP4-oxidative stress cascade. Br. J. Pharmacol. 170, 1190-1198
37. Karaca, Ü., Schram, M. T., Houben, A. J., Muris, D. M. and Stehouwer, C. D. (2014) Microvascular dysfunction as a link between obesity, insulin resistance and hypertension. Diabetes Res. Clin. Pract. 103, 382-387
38. Zhang, L., Gong, D., Li, S. and Zhou, X. (2012) Meta-analysis of the effects of statin therapy on endothelial function in patients with diabetes mellitus. Atherosclerosis 223, 78-85
39. Murrow, J. R., Sher, S., Ali, S., Uphoff, I., Patel, R., Porkert, M., Le, N. A., Jones, D. and Quyyumi, A. A. (2012) The differential effect of statins on oxidative stress and endothelial function: atorvastatin versus pravastatin. J. Clin. Lipidol. 6, 42-49
40. Violi, F., Carnevale, R., Pastori, D. and Pignatelli, P. (2014) Antioxidant and antiplatelet effects of atorvastatin by Nox2 inhibition. Trends Cardiovasc. Med. 24, 142-148
41. Baba, T. T., Ohara-Nemoto, Y., Miyazaki, T. and Nemoto, T. K. (2013) Involvement of geranylgeranylation of Rho and Rac GTPases in adipogenic and RANKL expression, which was inhibited by simvastatin. Cell Biochem. Funct. 31, 652-659
42. Vecchione, C., Gentile, M. T., Aretini, A., Marino, G., Poulet, R., Maffei, A., Passarelli, F., Landolfi, A., Vasta, A. and Lembo, G. (2007) A novel mechanism of action for statins against diabetes-induced oxidative stress. Diabetologia 50, 874-880
43. Li, J., Zhu, H., Shen, E., Wan, L., Arnold, J. M. and Peng, T. (2010) Deficiency of rac1 blocks NADPH oxidase activation, inhibits endoplasmic reticulum stress, and reduces myocardial remodeling in a mouse model of type 1 diabetes. Diabetes 59, 2033-2042
44. Sedeek, M., Gutsol, A., Montezano, A. C., Burger, D., Nguyen Dinh Cat, A., Kennedy, C. R., Burns, K. D., Cooper, M. E., Jandeleit-Dahm, K., Page, P. et al. (2013) Renoprotective effects of a novel Nox1/4 inhibitor in a mouse model of Type 2 diabetes. Clin. Sci. 124, 191-202
45. Sukumar, P., Viswambharan, H., Imrie, H., Cubbon, R. M., Yuldasheva, N., Gage, M., Galloway, S., Skromna, A., Kandavelu, P., Santos, C. X. et al. (2013) Nox2 NADPH oxidase has a critical role in insulin resistance-related endothelial cell dysfunction. Diabetes 62, 2130-2134
46. Sedeek, M., Montezano, A. C., Hebert, R. L., Gray, S. P., Di Marco, E., Jha, J. C., Cooper, M. E., Jandeleit-Dahm, K., Schiffrin, E. L., Wilkinson-Berka, J. L. and Touyz, R. M. (2012) Oxidative stress, Nox isoforms and complications of diabetes-potential targets for novel therapies. J. Cardiovasc. Transl. Res. 5, 509-518
47. Tanaka, S., Fukumoto, Y., Nochioka, K., Minami, T., Kudo, S., Shiba, N., Takai, Y., Williams, C. L., Liao, J. K. and Shimokawa, H. (2013) Statins exert the pleiotropic effects through small GTP-binding protein dissociation stimulator upregulation with a resultant Rac1 degradation. Arterioscler. Thromb. Vasc. Biol. 33, 1591-1600
48. Kaminska, B. (2005) MAPK signalling pathways as molecular targets for anti-inflammatory therapy from molecular mechanisms to therapeutic benefits. Biochim. Biophys. Acta 1754, 253-262
49. Montezano, A. C. and Touyz, R. M. (2014) Reactive oxygen species, vascular Noxs, and hypertension: focus on translational and clinical research. Antioxid. Redox Signal. 20, 164-182
50. Cuadrado, A., Martín-Moldes, Z., Ye, J. and Lastres-Becker, I. (2014) Transcription factors NRF2 and NF-κB are coordinated effectors of the Rho family, GTP-binding protein RAC1 during inflammation. J. Biol. Chem. 289, 15244-15258
51. Gong, X., Ma, Y., Ruan, Y., Fu, G. and Wu, S. (2014) Long-term atorvastatin improves age-related endothelial dysfunction by ameliorating oxidative stress and normalizing eNOS/iNOS imbalance in rat aorta. Exp. Gerontol. 52, 9-17
52. Song, L., Yang, Y. J., Dong, Q. T., Qian, H. Y., Gao, R. L., Qiao, S. B., Shen, R., He, Z. X., Lu, M. J., Zhao, S. H. et al. (2103) Atorvastatin enhance efficacy of mesenchymal stem cells treatment for swine myocardial infarction via activation of nitric oxide synthase. PLoS ONE 8, e65702
53. Kanda, M., Satoh, K. and Ichihara, K. (2003) Effects of atorvastatin and pravastatin on glucose tolerance in diabetic rats mildly induced by streptozotocin. Biol. Pharm. Bull. 26, 1681-1684
54. Madhu, S. V., Aslam, M., Galav, V., Bhattacharya, S. K. and Jafri, A. A. (2014) Atorvastatin prevents type 2 diabetes mellitus-an experimental study. Eur. J. Pharmacol. 728, 135-140
55. Huptas, S., Geiss, H. C., Otto, C. and Parhofer, K. G. (2006) Effect of atorvastatin (10 mg/day) on glucose metabolism in patients with the metabolic syndrome. Am. J. Cardiol. 98, 66-69
56. Erqou, S., Lee, C. C. and Adler, A. I. (2014) Statins and glycaemic control in individuals with diabetes: a systematic review and meta-analysis. Diabetologia 57, 2444-2452
57. Skoumas, J., Liontou, C., Chrysohoou, C., Masoura, C., Aznaouridis, K., Pitsavos, C. and Stefanadis, C. (2014) Statin therapy and risk of diabetes in patients with heterozygous familial hypercholesterolemia or familial combined hyperlipidemia. Atherosclerosis 237, 140-145
58. Aiman, U., Najmi, A. and Khan, R. A. (2014) Statin induced diabetes and its clinical implications. J. Pharmacol. Pharmacother. 5, 181-185
59. Preiss, D., Seshasai, S. R., Welsh, P., Murphy, S. A., Ho, J. E., Waters, D. D., DeMicco, D. A., Barter, P., Cannon, C. P., Sabatine, M. S. et al. (2011) Risk of incident diabetes with intensive-dose compared with moderate-dose statin therapy: a meta-analysis. JAMA 305, 2556-2564