The SIRT1 activator SRT1720 reverses vascular endothelial dysfunction, excessive superoxide production, and inflammation with aging in mice

American Journal of Physiology - Heart and Circulatory Physiology

Volumn 307, Issue 12, 2014, Pages H1754-H1763

  Gano, Lindsey B ^a   Donato, Anthony J ^a,b,c   Pasha, Hamza M ^a   Hearon, Christopher M ^a   Sindler, Amy L ^a   Seals, Douglas R ^a  

^a UNIVERSITY OF COLORADO   (United States)

^b UNIVERSITY OF UTAH SCHOOL OF MEDICINE   (United States)

^c VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Aging; COX 2 dilation; SIRT1; Superoxide; Vascular inflammation

Indexed keywords

CYCLOOXYGENASE 2; IMMUNOGLOBULIN ENHANCER BINDING PROTEIN; N [2 [3 (1 PIPERAZINYLMETHYL)IMIDAZO[2,1 B]THIAZOL 6 YL]PHENYL] 2 QUINOXALINECARBOXAMIDE; NITRIC OXIDE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 4; SUPEROXIDE; TUMOR NECROSIS FACTOR ALPHA; AMINE OXIDE; ANTIOXIDANT; FUSED HETEROCYCLIC RINGS; NOX4 PROTEIN, MOUSE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; SIRT1 PROTEIN, MOUSE; SIRTUIN 1; SPIN LABELING; TEMPOL;

AGED; AGING; ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; AORTA; ARTERY DIAMETER; ARTICLE; BIOAVAILABILITY; BODY MASS; CONTROLLED STUDY; ENDOTHELIAL DYSFUNCTION; EX VIVO STUDY; GROUPS BY AGE; HEART VOLUME; MALE; MOUSE; NONHUMAN; OXIDATIVE STRESS; PROTEIN EXPRESSION; VASCULAR ENDOTHELIUM; VASODILATATION; ANIMAL; DRUG EFFECTS; GENETICS; GROWTH, DEVELOPMENT AND AGING; INFLAMMATION; METABOLISM; PHYSIOLOGY; SPIN LABELING;

AGING; ANIMALS; ANTIOXIDANTS; CYCLIC N-OXIDES; CYCLOOXYGENASE 2; ENDOTHELIUM, VASCULAR; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; INFLAMMATION; MALE; MICE; NADPH OXIDASE; NF-KAPPA B; NITRIC OXIDE; SIRTUIN 1; SPIN LABELS; TUMOR NECROSIS FACTOR-ALPHA; VASODILATION;

EID: 84918836448     PISSN: 03636135     EISSN: 15221539     Source Type: Journal    
DOI: 10.1152/ajpheart.00377.2014     Document Type: Article

References (56)

1. Alcendor RR, Gao S, Zhai P, Zablocki D, Holle E, Yu X, Tian B, Wagner T, Vatner SF, Sadoshima J. Sirt1 regulates aging and resistance to oxidative stress in the heart. Circ Res 100: 1512-1521, 2007.
2. Blackwell KA, Sorenson JP, Richardson DM, Smith LA, Suda O, Nath K, Katusic ZS. Mechanisms of aging-induced impairment of endothelium-dependent relaxation: role of tetrahydrobiopterin. Am J Physiol Heart Circ Physiol 287: H2448-H2453, 2004.
3. Cawello W, Schweer H, Muller R, Bonn R, Seyberth HW. Metabolism and pharmacokinetics of prostaglandin E1 administered by intravenous infusion in human subjects. Eur J Clin Pharmacol 46: 275-277, 1994.
4. Chang HC, Guarente L. SIRT1 and other sirtuins in metabolism. Trends Endocrinol Metab 25: 138-145, 2014.
5. Chen LF, Williams SA, Mu Y, Nakano H, Duerr JM, Buckbinder L, Greene WC. NF-kappaB RelA phosphorylation regulates RelA acetylation. Mol Cell Biol 25: 7966-7975, 2005.
6. Chung HY, Sung B, Jung KJ, Zou Y, Yu BP. The molecular inflammatory process in aging. Antioxid Redox Signal 8: 572-581, 2006.
7. Csiszar A, Labinskyy N, Podlutsky A, Kaminski PM, Wolin MS, Zhang C, Mukhopadhyay P, Pacher P, Hu F, de Cabo R, Ballabh P, Ungvari Z. Vasoprotective effects of resveratrol and SIRT1: attenuation of cigarette smoke-induced oxidative stress and proinflammatory phenotypic alterations. Am J Physiol Heart Circ Physiol 294: H2721-H2735, 2008.
8. Csiszar A, Ungvari Z, Koller A, Edwards JG, Kaley G. Aging-induced proinflammatory shift in cytokine expression profile in coronary arteries. FASEB J 17: 1183-1185, 2003.
9. d'Uscio LV, Smith LA, Santhanam AV, Richardson D, Nath KA, Katusic ZS. Essential role of endothelial nitric oxide synthase in vascular effects of erythropoietin. Hypertension 49: 1142-1148, 2007.
10. Dai H, Kustigian L, Carney D, Case A, Considine T, Hubbard BP, Perni RB, Riera TV, Szczepankiewicz B, Vlasuk GP, Stein RL. SIRT1 activation by small molecules: kinetic and biophysical evidence for direct interaction of enzyme and activator. J Biol Chem 285: 32695-32703, 2010.
11. Didion SP, Ryan MJ, Didion LA, Fegan PE, Sigmund CD, Faraci FM. Increased superoxide and vascular dysfunction in CuZnSOD-deficient mice. Circ Res 91: 938-944, 2002.
12. Donato AJ, Black AD, Jablonski KL, Gano LB, Seals DR. Aging is associated with greater nuclear NFkappaB, reduced IkappaBalpha, and increased expression of proinflammatory cytokines in vascular endothelial cells of healthy humans. Aging Cell 7: 805-812, 2008.
13. Donato AJ, Magerko KA, Lawson BR, Durrant JR, Lesniewski LA, Seals DR. SIRT-1 and vascular endothelial dysfunction with ageing in mice and humans. J Physiol 589: 4545-4554, 2011.
14. Durrant JR, Seals DR, Connell ML, Russell MJ, Lawson BR, Folian BJ, Donato AJ, Lesniewski LA. Voluntary wheel running restores endothelial function in conduit arteries of old mice: direct evidence for reduced oxidative stress, increased superoxide dismutase activity and down-regulation of NADPH oxidase. J Physiol 587: 3271-3285, 2009.
15. Feige JN, Lagouge M, Canto C, Strehle A, Houten SM, Milne JC, Lambert PD, Mataki C, Elliott PJ, Auwerx J. Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. Cell Metab 8: 347-358, 2008.
16. Fleenor BS, Marshall KD, Durrant JR, Lesniewski LA, Seals DR. Arterial stiffening with ageing is associated with transforming growth factor-beta1-related changes in adventitial collagen: reversal by aerobic exercise. J Physiol 588: 3971-3982, 2010.
17. Fleenor BS, Seals DR, Zigler ML, Sindler AL. Superoxide-lowering therapy with TEMPOL reverses arterial dysfunction with aging in mice. Aging Cell 11: 269-276, 2012.
18. Fleenor BS, Sindler AL, Marvi NK, Howell KL, Zigler ML, Yoshizawa M, Seals DR. Curcumin ameliorates arterial dysfunction and oxidative stress with aging. Exp Gerontol 48: 269-276, 2013.
19. Gendron ME, Thorin-Trescases N, Villeneuve L, Thorin E. Aging associated with mild dyslipidemia reveals that COX-2 preserves dilation despite endothelial dysfunction. Am J Physiol Heart Circ Physiol 292: H451-H458, 2007.
20. Gioscia-Ryan RA, LaRocca TJ, Sindler AL, Zigler MC, Murphy MP, Seals DR. Mitochondria-targeted antioxidant (MitoQ) ameliorates agerelated arterial endothelial dysfunction in mice. J Physiol 592: 2549-2561, 2014.
21. Hamilton CA, Brosnan MJ, McIntyre M, Graham D, Dominiczak AF. Superoxide excess in hypertension and aging: a common cause of endothelial dysfunction. Hypertension 37: 529-534, 2001.
22. He W, Wang Y, Zhang MZ, You L, Davis LS, Fan H, Yang HC, Fogo AB, Zent R, Harris RC, Breyer MD, Hao CM. Sirt1 activation protects the mouse renal medulla from oxidative injury. J Clin Invest 120: 1056-1068, 2010.
23. Hubbard BP, Gomes AP, Dai H, Li J, Case AW, Considine T, Riera TV, Lee JE, ESY, Lamming DW, Pentelute BL, Schuman ER, Stevens LA, Ling AJ, Armour SM, Michan S, Zhao H, Jiang Y, Sweitzer SM, Blum CA, Disch JS, Ng PY, Howitz KT, Rolo AP, Hamuro Y, Moss J, Perni RB, Ellis JL, Vlasuk GP, Sinclair DA. Evidence for a common mechanism of SIRT1 regulation by allosteric activators. Science 339: 1216-1219, 2013.
24. Kao CL, Chen LK, Chang YL, Yung MC, Hsu CC, Chen YC, Lo WL, Chen SJ, Ku HH, Hwang SJ. Resveratrol protects human endothelium from H(2)O(2)-induced oxidative stress and senescence via SirT1 activation. J Atheroscler Thromb 17: 970-979, 2010.
25. Kawabe J, Ushikubi F, Hasebe N. Prostacyclin in vascular diseases. Recent insights and future perspectives. Circulation 74: 836-843, 2010.
26. Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: Part I: aging arteries: a "set up" for vascular disease. Circulation 107: 139-146, 2003.
27. Lesniewski LA, Connell ML, Durrant JR, Folian BJ, Anderson MC, Donato AJ, Seals DR. B6D2F1 Mice are a suitable model of oxidative stress-mediated impaired endothelium-dependent dilation with aging. J Gerontol A Biol Sci Med Sci 64: 9-20, 2009.
28. Lesniewski LA, Durrant JR, Connell ML, Folian BJ, Donato AJ, Seals DR. Salicylate treatment improves age-associated vascular endothelial dysfunction: potential role of nuclear factor kappaB and forkhead Box O phosphorylation. J Gerontol A Biol Sci Med Sci 66: 409-418, 2011.
29. Li L, Smith A, Hagen TM, Frei B. Vascular oxidative stress and inflammation increase with age: ameliorating effects of alpha-lipoic acid supplementation. Ann NY Acad Sci 1203: 151-159, 2010.
30. Mattagajasingh I, Kim CS, Naqvi A, Yamamori T, Hoffman TA, Jung SB, DeRicco J, Kasuno K, Irani K. SIRT1 promotes endotheliumdependent vascular relaxation by activating endothelial nitric oxide synthase. Proc Natl Acad Sci USA 104: 14855-14860, 2007.
31. Menssen A, Hydbring P, Kapelle K, Vervoorts J, Diebold J, Luscher B, Larsson LG, Hermeking H. The c-MYC oncoprotein, the NAMPT enzyme, the SIRT1-inhibitor DBC1, and the SIRT1 deacetylase form a positive feedback loop. Proc Natl Acad Sci USA 109: E187-196, 2012.
32. Milne JC, Lambert PD, Schenk S, Carney DP, Smith JJ, Gagne DJ, Jin L, Boss O, Perni RB, Vu CB, Bemis JE, Xie R, Disch JS, Ng PY, Nunes JJ, Lynch AV, Yang H, Galonek H, Israelian K, Choy W, Iffland A, Lavu S, Medvedik O, Sinclair DA, Olefsky JM, Jirousek MR, Elliott PJ, Westphal CH. Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes. Nature 450: 712-716, 2007.
33. Minor RK, Baur JA, Gomes AP, Ward TM, Csiszar A, Mercken EM, Abdelmohsen K, Shin YK, Canto C, Scheibye-Knudsen M, Krawczyk M, Irusta PM, Martin-Montalvo A, Hubbard BP, Zhang Y, Lehrmann E, White AA, Price NL, Swindell WR, Pearson KJ, Becker KG, Bohr VA, Gorospe M, Egan JM, Talan MI, Auwerx J, Westphal CH, Ellis JL, Ungvari Z, Vlasuk GP, Elliott PJ, Sinclair DA, de Cabo R. SRT1720 improves survival and healthspan of obese mice. Sci Rep 1: 70, 2011.
34. Mitchell SJ, Martin-Montalvo A, Mercken EM, Palacios HH, Ward TM, Abulwerdi G, Minor RK, Vlasuk GP, Ellis JL, Sinclair DA, Dawson J, Allison DB, Zhang Y, Becker KG, Bernier M, de Cabo R. The SIRT1 activator SRT1720 extends lifespan and improves health of mice fed a standard diet. Cell Rep 6: 836-843, 2014.
35. Muller-Delp JM, Spier SA, Ramsey MW, Delp MD. Aging impairs endothelium-dependent vasodilation in rat skeletal muscle arterioles. Am J Physiol Heart Circ Physiol 283: H1662-H1672, 2002.
36. Rippe C, Lesniewski L, Connell M, LaRocca T, Donato A, Seals D. Short-term calorie restriction reverses vascular endothelial dysfunction in old mice by increasing nitric oxide and reducing oxidative stress. Aging Cell 9: 304-312, 2010.
37. Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, Borden WB, Bravata DM, Dai S, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Soliman EZ, Sorlie PD, Sotoodehnia N, Turan TN, Virani SS, Wong ND, Woo D, Turner MB. Heart disease and stroke statistics-2012 update: a report from the American Heart Association. Circulation 125: e2-e220, 2012.
38. Rolland PH, Jouve R, Pellegrin E, Mercier C, Serradimigni A. Alteration in prostacyclin and prostaglandin E2 production. Correlation with changes in human aortic atherosclerotic disease. Arteriosclerosis 4: 70-78, 1984.
39. Sindler AL, Fleenor BS, Calvert JW, Marshall KD, Zigler ML, Lefer DJ, Seals DR. Nitrite supplementation reverses vascular endothelial dysfunction and large elastic artery stiffness with aging. Aging Cell 10: 429-437, 2011.
40. Singh N, Prasad S, Singer DR, MacAllister RJ. Ageing is associated with impairment of nitric oxide and prostanoid dilator pathways in the human forearm. Clin Sci 102: 595-600, 2002.
41. Smoliga JM, Vang O, Baur JA. Challenges of translating basic research into therapeutics: resveratrol as an example. J Gerontol A Biol Sci Med Sci 67: 158-167, 2012.
42. Spanier G, Xu H, Xia N, Tobias S, Deng S, Wojnowski L, Forstermann U, Li H. Resveratrol reduces endothelial oxidative stress by modulating the gene expression of superoxide dismutase 1 (SOD1), glutathione peroxidase 1 (GPx1) and NADPH oxidase subunit (Nox4). J Physiol Pharmacol 60, Suppl 4: 111-116, 2009.
43. Spier SA, Delp MD, Stallone JN, Dominguez JM 2nd, Muller-Delp JM. Exercise training enhances flow-induced vasodilation in skeletal muscle resistance arteries of aged rats: role of PGI2 and nitric oxide. Am J Physiol Heart Circ Physiol 292: H3119-H3127, 2007.
44. Sun D, Liu H, Yan C, Jacobson A, Ojaimi C, Huang A, Kaley G. COX-2 contributes to the maintenance of flow-induced dilation in arterioles of eNOS-knockout mice. Am J Physiol Heart Circ Physiol 291: H1429-H1435, 2006.
45. Taddei S, Virdis A, Ghiadoni L, Salvetti G, Bernini G, Magagna A, Salvetti A. Age-related reduction of NO availability and oxidative stress in humans. Hypertension 38: 274-279, 2001.
46. Thengchaisri N, Kuo L. Hydrogen peroxide induces endothelium-dependent and-independent coronary arteriolar dilation: role of cyclooxygenase and potassium channels. Am J Physiol Heart Circ Physiol 285: H2255-H2263, 2003.
47. Tong C, Morrison A, Mattison S, Qian S, Bryniarski M, Rankin B, Wang J, Thomas DP, Li J. Impaired SIRT1 nucleocytoplasmic shuttling in the senescent heart during ischemic stress. FASEB J 27: 4332-4342, 2013.
48. Ungvari Z, Labinskyy N, Gupte S, Chander PN, Edwards JG, Csiszar A. Dysregulation of mitochondrial biogenesis in vascular endothelial and smooth muscle cells of aged rats. Am J Physiol Heart Circ Physiol 294: H2121-H2128, 2008.
49. Ungvari Z, Labinskyy N, Mukhopadhyay P, Pinto JT, Bagi Z, Ballabh P, Zhang C, Pacher P, Csiszar A. Resveratrol attenuates mitochondrial oxidative stress in coronary arterial endothelial cells. Am J Physiol Heart Circ Physiol 297: H1876-H1881, 2009.
50. Woodman CR, Price EM, Laughlin MH. Selected Contribution: aging impairs nitric oxide and prostacyclin mediation of endothelium-dependent dilation in soleus feed arteries. J Appl Physiol 95: 2164-2170, 2003.
51. Xiong S, Salazar G, Patrushev N, Alexander RW. FoxO1 mediates an autofeedback loop regulating SIRT1 expression. J Biol Chem 286: 5289-5299, 2011.
52. Yang H, Zhang W, Pan H, Feldser HG, Lainez E, Miller C, Leung S, Zhong Z, Zhao H, Sweitzer S, Considine T, Riera T, Suri V, White B, Ellis JL, Vlasuk GP, Loh C. SIRT1 activators suppress inflammatory responses through promotion of p65 deacetylation and inhibition of NF-kappaB activity. PLoS One 7: e46364, 2012.
53. Yoshizaki T, Milne JC, Imamura T, Schenk S, Sonoda N, Babendure JL, Lu JC, Smith JJ, Jirousek MR, Olefsky JM. SIRT1 exerts antiinflammatory effects and improves insulin sensitivity in adipocytes. Mol Cell Biol 29: 1363-1374, 2009.
54. Yoshizaki T, Schenk S, Imamura T, Babendure JL, Sonoda N, Bae EJ, Oh DY, Lu M, Milne JC, Westphal C, Bandyopadhyay G, Olefsky JM. SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity. Am J Physiol Endocrinol Metab 298: E419-E428, 2010.
55. Zarzuelo MJ, Lopez-Sepulveda R, Sanchez M, Romero M, Gomez-Guzman M, Ungvary Z, Perez-Vizcaino F, Jimenez R, Duarte J. SIRT1 inhibits NADPH oxidase activation and protects endothelial function in the rat aorta: implications for vascular aging. Biochem Pharmacol 85: 1288-1296, 2013.
56. Zhang QJ, Wang Z, Chen HZ, Zhou S, Zheng W, Liu G, Wei YS, Cai H, Liu DP, Liang CC. Endothelium-specific overexpression of class III deacetylase SIRT1 decreases atherosclerosis in apolipoprotein E-deficient mice. Cardiovasc Res 80: 191-199, 2008.