Mitochondrial redox plays a critical role in the paradoxical effects of NAPDH oxidase-derived ROS on coronary endothelium

Cardiovascular Research

Volumn 113, Issue 2, 2017, Pages 234-246

  Shafique, Ehtesham ^a   Torina, Anali ^a   Reichert, Karla ^a   Colantuono, Bonnie ^a   Nur, Nasifa ^a   Zeeshan, Khawaja ^a   Ravichandran, Vani ^a   Liu, Yuhong ^a,b   Feng, Jun ^a,b   Benjamin, Laura E ^c   Irani, Kaikobad ^d   Harrington, Elizabeth O ^e,f   Sellke, Frank W ^a,b   Ruhul Abid, Md ^a,b,f  

^a RHODE ISLAND HOSPITAL   (United States)

^b BROWN UNIVERSITY   (United States)

^c ELI LILLY AND COMPANY   (United States)

^d UNIVERSITY OF IOWA   (United States)

^e VETERANS AFFAIRS MEDICAL CENTER   (United States)

^f BROWN UNIVERSITY   (United States)

Author keywords

Endothelium; NADPH oxidase; Nitric oxide; Reactive oxygen species; Signal transduction

Indexed keywords

3 NITROTYROSINE; DRINKING WATER; ENDOTHELIAL NITRIC OXIDE SYNTHASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MANGANESE SUPEROXIDE DISMUTASE; NITRIC OXIDE; REACTIVE OXYGEN METABOLITE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE PHOSPHATE OXIDASE 2; TETRACYCLINE; VASCULAR ENDOTHELIAL CADHERIN; 3-NITROTYROSINE; ANGIOGENIC FACTOR; CADHERIN; LEUKOCYTE ANTIGEN; NOS3 PROTEIN, MOUSE; SUPEROXIDE DISMUTASE; TYROSINE; VASODILATOR AGENT;

ANGIOGENESIS; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; BLOOD VESSEL FUNCTION; CARDIAC MUSCLE CELL; CELL PROLIFERATION; COMPARATIVE STUDY; CONTROLLED STUDY; CORONARY ARTERY DILATATION; CORONARY BLOOD VESSEL; CYTOSOL; ENZYME ACTIVATION; ENZYME ACTIVITY; ISOLATED HEART; LONG TERM EXPOSURE; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRIAL RESPIRATION; MOUSE; NONHUMAN; PRIORITY JOURNAL; TRANSGENIC MOUSE; VASCULAR ENDOTHELIUM; ANALOGS AND DERIVATIVES; ANIMAL; CELL CULTURE; DOSE RESPONSE; DRUG EFFECTS; ENDOTHELIUM CELL; ENZYMOLOGY; GENETICS; GENOTYPE; IN VITRO STUDY; METABOLISM; MITOCHONDRION; OXIDATION REDUCTION REACTION; PHENOTYPE; PHOSPHORYLATION; SIGNAL TRANSDUCTION; TIME FACTOR; VASODILATATION;

AMP-ACTIVATED PROTEIN KINASES; ANGIOGENESIS INDUCING AGENTS; ANIMALS; ANTIGENS, CD; CADHERINS; CELL PROLIFERATION; CELLS, CULTURED; CORONARY VESSELS; DOSE-RESPONSE RELATIONSHIP, DRUG; ENDOTHELIAL CELLS; ENZYME ACTIVATION; GENOTYPE; IN VITRO TECHNIQUES; MEMBRANE POTENTIAL, MITOCHONDRIAL; MICE, TRANSGENIC; MITOCHONDRIA; NADPH OXIDASE; NEOVASCULARIZATION, PHYSIOLOGIC; NITRIC OXIDE; NITRIC OXIDE SYNTHASE TYPE III; OXIDATION-REDUCTION; PHENOTYPE; PHOSPHORYLATION; REACTIVE OXYGEN SPECIES; SIGNAL TRANSDUCTION; SUPEROXIDE DISMUTASE; TIME FACTORS; TYROSINE; VASODILATION; VASODILATOR AGENTS;

EID: 85015242649     PISSN: 00086363     EISSN: 17553245     Source Type: Journal    
DOI: 10.1093/cvr/cvw249     Document Type: Article

References (82)

1. San Martin A, Griendling KK. NADPH oxidases: progress and opportunities. Antioxid Redox Signal 2014;20:2692-2694.
2. Harrison D, Griendling KK, Landmesser U, Hornig B, Drexler H. Role of oxidative stress in atherosclerosis. Am J Cardiol 2003;91:7A-11A.
3. Irani K. Oxidant signaling in vascular cell growth, death, and survival: a review of the roles of reactive oxygen species in smooth muscle and endothelial cell mitogenic and apoptotic signaling. Circ Res 2000;87:179-183.
4. Abid MR, Tsai JC, Spokes KC, Deshpande SS, Irani K, Aird WC. Vascular endothelial growth factor induces manganese-superoxide dismutase expression in endothelial cells by a Rac1-regulated NADPH oxidase-dependent mechanism. FASEB J 2001;15:2548-2550.
5. Moldovan L, Irani K, Moldovan NI, Finkel T, Goldschmidt-Clermont PJ. The actin cytoskeleton reorganization induced by Rac1 requires the production of superoxide. Antioxid Redox Signal 1999;1:29-43.
6. Ushio-Fukai M, Tang Y, Fukai T, Dikalov SI, Ma Y, Fujimoto M, Quinn MT, Pagano PJ, Johnson C, Alexander RW. Novel role of gp91(phox)-containing NAD(P)H oxidase in vascular endothelial growth factor-induced signaling and angiogenesis. Circ Res 2002;91:1160-1167.
7. Bayraktutan U, Blayney L, Shah AM. Molecular characterization and localization of the NAD(P)H oxidase components gp91-phox and p22-phox in endothelial cells. Arterioscler Thromb Vasc Biol 2000;20:1903-1911.
8. Spiekermann S, Landmesser U, Dikalov S, Bredt M, Gamez G, Tatge H, Reepschlager N, Hornig B, Drexler H, Harrison DG. Electron spin resonance characterization of vascular xanthine and NAD(P)H oxidase activity in patients with coronary artery disease: relation to endothelium-dependent vasodilation. Circulation 2003;107:1383-1389.
9. Alami R, Greally JM, Tanimoto K, Hwang S, Feng YQ, Engel JD, Fiering S, Bouhassira EE. Beta-globin YAC transgenes exhibit uniform expression levels but position effect variegation in mice. Hum Mol Genet 2000;9:631-636.
10. Arbiser JL, Petros J, Klafter R, Govindajaran B, McLaughlin ER, Brown LF, Cohen C, Moses M, Kilroy S, Arnold RS, Lambeth JD. Reactive oxygen generated by Nox1 triggers the angiogenic switch. Proc Natl Acad Sci USA 2002;99:715-720.
11. Mollnau H, Wendt M, Szocs K, Lassegue B, Schulz E, Oelze M, Li H, Bodenschatz M, August M, Kleschyov AL, Tsilimingas N, Walter U, Forstermann U, Meinertz T, Griendling K, Munzel T. Effects of angiotensin II infusion on the expression and func-tion of NAD(P)H oxidase and components of nitric oxide/cGMP signaling. Circ Res 2002;90:E58-E65.
12. Higashi M, Shimokawa H, Hattori T, Hiroki J, Mukai Y, Morikawa K, Ichiki T, Takahashi S, Takeshita A. Long-term inhibition of Rho-kinase suppresses angiotensin II-induced cardiovascular hypertrophy in rats in vivo: effect on endothelial NAD(P)H oxidase system. Circ Res 2003;93:767-775.
13. Brandes RP. Role of NADPH oxidases in the control of vascular gene expression. Antioxid Redox Signal 2003;5:803-811.
14. Kobayashi S, Nojima Y, Shibuya M, Maru Y. Nox1 regulates apoptosis and potentially stimulates branching morphogenesis in sinusoidal endothelial cells. Exp Cell Res 2004;300:455-462.
15. Petry A, Djordjevic T, Weitnauer M, Kietzmann T, Hess J, Gorlach A. NOX2 and NOX4 mediate proliferative response in endothelial cells. Antioxid Redox Signal 2006;8:1473-1484.
16. Van Buul JD, Fernandez-Borja M, Anthony EC, Hordijk PL. Expression and localization of NOX2 and NOX4 in primary human endothelial cells. Antioxid Redox Signal 2005;7:308-317.
17. McNally JS, Saxena A, Cai H, Dikalov S, Harrison DG. Regulation of xanthine oxidor-eductase protein expression by hydrogen peroxide and calcium. Arterioscler Thromb Vasc Biol 2005;25:1623-1628.
18. Li JM, Shah AM. ROS generation by nonphagocytic NADPH oxidase: potential relevance in diabetic nephropathy. J Am Soc Nephrol 2003;14:S221-S226.
19. Lassegue B, Griendling KK. NADPH oxidases: functions and pathologies in the vascu-lature. Arterioscler Thromb Vasc Biol 2010;30:653-661.
20. Datla SR, Griendling KK. Reactive oxygen species, NADPH oxidases, and hypertension. Hypertension 2010;56:325-330.
21. Luo Z, Teerlink T, Griendling K, Aslam S, Welch WJ, Wilcox CS. Angiotensin II and NADPH oxidase increase ADMA in vascular smooth muscle cells. Hypertension 2010;56:498-504.
22. Fukai T, Ushio-Fukai M. Superoxide dismutases: role in redox signaling, vascular function, and diseases. Antioxid Redox Signal 2011;15:1583-1606.
23. Frey RS, Ushio-Fukai M, Malik AB. NADPH oxidase-dependent signaling in endothe-lial cells: role in physiology and pathophysiology. Antioxid Redox Signal 2009;11:791-810.
24. Drummond GR, Selemidis S, Griendling KK, Sobey CG. Combating oxidative stress in vascular disease: NADPH oxidases as therapeutic targets. Nat Rev Drug Discov 2011;10:453-471.
25. Willcox BJ, Curb JD, Rodriguez BL. Antioxidants in cardiovascular health and disease: key lessons from epidemiologic studies. Am J Cardiol 2008;101:75D-86D.
26. Vivekananthan DP, Penn MS, Sapp SK, Hsu A, Topol EJ. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet 2003;361:2017-2023.
27. Virtamo J, Rapola JM, Ripatti S, Heinonen OP, Taylor PR, Albanes D, Huttunen JK. Effect of vitamin E and beta carotene on the incidence of primary nonfatal myocardial infarction and fatal coronary heart disease. Arch Intern Med 1998;158:668-675.
28. Hegele RA. Angiotensin-converting enzyme (ACE) inhibition in the secondary prevention of vascular disease: the Heart Outcomes Prevention Evaluation (HOPE) Trial and its substudies. Curr Atheroscler Rep 2000;2:361-362.
29. Bjelakovic G, Nikolova D, Gluud LL, Simonetti RG, Gluud C. Mortality in randomized trials of antioxidant supplements for primary and secondary prevention: systematic review and meta-analysis. JAMA 2007;297:842-857.
30. Bagi Z, Feher A, Beleznai T. Preserved coronary arteriolar dilatation in patients with type 2 diabetes mellitus: implications for reactive oxygen species. Pharmacol Rep 2009;61:99-104.
31. Dao VT, Casas AI, Maghzal GJ, Seredenina T, Kaludercic N, Robledinos-Anton N, Di Lisa F Stocker, R Ghezzi, P Jaquet, V Cuadrado, A Schmidt, HH. Pharmacology and clinical drug candidates in redox medicine. Antioxid Redox Signal 2015;23:1113-1129.
32. Schmidt HHHW, Stocker R, Vollbracht C, Paulsen G, Riley D, Daiber A, Cuadrado A. Antioxidants in translational medicine. Antioxid Redox Signal 2015;23:1130-1143.
33. Feng J, Damrauer SM, Lee M, Sellke FW, Ferran C, Abid R. Endothelium-dependent coronary vasodilatation requires NADPH oxidase-derived reactive oxygen species. Arterioscler Thromb Vasc Biol 2010;30:1703-1710.
34. Zhang Q, Malik P, Pandey D, Gupta S, Jagnandan D, Belin de Chantemele E, Banfi B, Marrero MB, Rudic RD, Stepp DW, Fulton DJ. Paradoxical activation of endothelial nitric oxide synthase by NADPH oxidase. Arterioscler Thromb Vasc Biol 2008;28:1627-1633.
35. Shafique E, Choy WC, Liu Y, Feng J, Cordeiro B, Lyra A, Arafah M, Yassin-Kassab A, Zanetti A V, Clements RT, Bianchi C, Benjamin LE, Sellke FW, Abid MR. Oxidative stress improves coronary endothelial function through activation of the pro-survival kinase AMPK. Aging (Albany NY) 2013;5:515-530.
36. Abid MR, Yano K, Guo S, Patel VI, Shrikhande G, Spokes KC, Ferran C, Aird WC. Forkhead transcription factors inhibit vascular smooth muscle cell proliferation and neointimal hyperplasia. J Biol Chem 2005;280:29864-29873.
37. Dharaneeswaran H, Abid MR, Yuan L, Dupuis D, Beeler D, Spokes KC, Janes L, Sciuto T, Kang PM, Jaminet SC, Dvorak A, Grant MA, Regan ER, Aird WC. FOXO1-mediated activation of Akt plays a critical role in vascular homeostasis. Circ Res 2014;115:238-251.
38. Zudaire E, Gambardella L, Kurcz C, Vermeren S. A computational tool for quantitative analysis of vascular networks. PLoS One 2011;6:e27385.
39. Griendling KK, Minieri CA, Ollerenshaw JD, Alexander RW. Angiotensin II stimulates NADH and NADPH oxidase activity in cultured vascular smooth muscle cells. Circ Res 1994;74:1141-1148.
40. Abid MR, Schoots IG, Spokes KC, Wu SQ, Mawhinney C, Aird WC. Vascular endo-thelial growth factor-mediated induction of manganese superoxide dismutase occurs through redox-dependent regulation of forkhead and IkappaB/NF-kappaB. J Biol Chem 2004;279:44030-44038.
41. Markvicheva KN, Bilan DS, Mishina NM, Gorokhovatsky AY, Vinokurov LM, Lukyanov S, Belousov VV. A genetically encoded sensor for H2O2 with expanded dynamic range. Bioorg Med Chem 2011;19:1079-1084.
42. Bilan DS, Belousov VV. HyPer family probes: state of the art. Antioxid Redox Signal 2016;24:731-751.
43. Abid MR, Shih S-C, Otu HH, Spokes KC, Okada Y, Curiel DT, Minami T, Aird WC. A novel class of vascular endothelial growth factor-responsive genes that require forkhead activity for expression. J Biol Chem 2006;281:35544-35553.
44. Correa RM, Lafayette SS, Pereira GJ, Hirata H, Garcez-do-Carmo L, Smaili SS. Mitochondrial involvement in carbachol-induced intracellular Ca2+ mobilization and contraction in rat gastric smooth muscle. Life Sci 2011;89:757-764.
45. Widlansky ME, Wang J, Shenouda SM, Hagen TM, Smith AR, Kizhakekuttu TJ, Kluge MA, Weihrauch D, Gutterman DD, Vita JA. Altered mitochondrial membrane potential, mass, and morphology in the mononuclear cells of humans with type 2 diabetes. Transl Res 2010;156:15-25.
46. Shenouda SM, Widlansky ME, Chen K, Xu G, Holbrook M, Tabit CE, Hamburg NM, Frame AA, Caiano TL, Kluge MA, Duess MA, Levit A, Kim B, Hartman ML, Joseph L, Shirihai OS, Vita JA. Altered mitochondrial dynamics contributes to endothelial dysfunction in diabetes mellitus. Circulation 2011;124:444-453.
47. Readnower RD, Brainard RE, Hill BG, Jones SP. Standardized bioenergetic profiling of adult mouse cardiomyocytes. Physiol Genomics 2012;44:1208-1213.
48. Clements RT, Cordeiro B, Feng J, Bianchi C, Sellke FW. Rottlerin increases cardiac contractile performance and coronary perfusion through BKca ++ channel activation after cold cardioplegic arrest in isolated hearts. Circulation 2011;124: S55-61.
49. Phung TL, Ziv K, Dabydeen D, Eyiah-Mensah G, Riveros M, Perruzzi C, Sun J, Monahan-Earley RA, Shiojima I, Nagy JA, Lin MI, Walsh K, Dvorak AM, Briscoe DM, Neeman M, Sessa WC, Dvorak HF, Benjamin LE. Pathological angiogenesis is induced by sustained Akt signaling and inhibited by rapamycin. Cancer Cell 2006;10:159-170.
50. Abid MR, Spokes KC, Shih S-C, Aird WC. NADPH oxidase activity selectively modulates vascular endothelial growth factor signaling pathways. J Biol Chem 2007;282:35373-35385.
51. Belousov VV, Fradkov AF, Lukyanov KA, Staroverov DB, Shakhbazov KS, Terskikh AV, Lukyanov S. Genetically encoded fluorescent indicator for intracellular hydrogen peroxide. Nat Methods 2006;3:281-286.
52. MacMillan-Crow LA, Thompson JA. Tyrosine modifications and inactivation of active site manganese superoxide dismutase mutant (Y34F) by peroxynitrite. Arch Biochem Biophys 1999;366:82-88.
53. Douglas G, Bendall JK, Crabtree MJ, Tatham AL, Carter EE, Hale AB, Channon KM. Endothelial-specific Nox2 overexpression increases vascular superoxide and macro-phage recruitment in ApoE(-)/(-) mice. Cardiovasc Res 2012;94:20-29.
54. Murdoch CE, Alom-Ruiz SP, Wang M, Zhang M, Walker S, Yu B, Brewer A, Shah AM. Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction. Basic Res Cardiol 2011;106:527-538.
55. Desler C, Lykke A, Rasmussen LJ. The effect of mitochondrial dysfunction on cyto-solic nucleotide metabolism. J Nucleic Acids 2010;2010:1-9.
56. Huang J, Hitt ND, Kleinberg ME. Stoichiometry of p22-phox and gp91-phox in phagocyte cytochrome b558. Biochemistry 1995;34:16753-16757.
57. Wallach TM, Segal AW, Wallach TM, Segal AW. Stoichiometry of the subunits of fla-vocytochrome b558 of the NADPH oxidase of phagocytes. Biochem J 1996;320:33-38.
58. Nakada D, Saunders TL, Morrison SJ. Lkb1 regulates cell cycle and energy metabolism in haematopoietic stem cells. Nature 2010;468:653-658.
59. Ojuka EO, Jones TE, Nolte LA, Chen M, Wamhoff BR, Sturek M, Holloszy JO. Regulation of GLUT4 biogenesis in muscle: evidence for involvement of AMPK and Ca(2+). Am J Physiol Endocrinol Metab 2002;282:E1008-E1013.
60. Wang XR, Zhang MW, Chen DD, Zhang Y, Chen AF. AMP-activated protein kinase rescues the angiogenic functions of endothelial progenitor cells via manganese super-oxide dismutase induction in type 1 diabetes. Am J Physiol Endocrinol Metab 2011;300:E1135-E1145.
61. Sun L, Zhao M, Yu XJ, Wang H, He X, Liu JK, Zang WJ. Cardioprotection by acetyl-choline: a novel mechanism via mitochondrial biogenesis and function involving the PGC-1alpha pathway. J Cell Physiol 2013;228:1238-1248.
62. Hardie DG, Ross FA, Hawley SA. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol 2012;13:251-262.
63. Gundewar S, Calvert JW, Jha S, Toedt-Pingel I, Ji SY, Nunez D, Ramachandran A, Anaya-Cisneros M, Tian R, Lefer DJ. Activation of AMP-activated protein kinase by metformin improves left ventricular function and survival in heart failure. Circ Res 2009;104:403-411.
64. Li L, Chen Y, Gibson SB. Starvation-induced autophagy is regulated by mitochondrial reactive oxygen species leading to AMPK activation. Cell Signal 2013;25:50-65.
65. Wang Q, Liang B, Shirwany NA, Zou MH. 2-Deoxy-D-glucose treatment of endothe-lial cells induces autophagy by reactive oxygen species-mediated activation of the AMP-activated protein kinase. PLoS One 2011;6:e17234.
66. Djafarzadeh S, Vuda M, Takala J, Jakob SM. Effect of remifentanil on mitochondrial oxygen consumption of cultured human hepatocytes. PLoS One 2012;7:e45195.
67. Namasivayam M, Adji A, O'Rourke MF. Influence of aortic pressure wave components determined noninvasively on myocardial oxygen demand in men and women. Hypertension 2011;57:193-200.
68. Frederich M, O'Rourke MR, Furey NB, Jost JA. AMP-activated protein kinase (AMPK) in the rock crab, Cancer irroratus: an early indicator of temperature stress. J Exp Biol 2009;212:722-730.
69. Dromparis P, Michelakis ED. Mitochondria in vascular health and disease. Annu Rev Physiol 2013;75:95-126.
70. Chen ZP, Mitchelhill KI, Michell BJ, Stapleton D, Rodriguez-Crespo I, Witters LA, Power DA, Ortiz de Montellano PR, Kemp BE. AMP-activated protein kinase phos-phorylation of endothelial NO synthase. FEBS Lett 1999;443:285-289.
71. Boo YC, Sorescu G, Boyd N, Shiojima I, Walsh K, Du J, Jo H. Shear stress stimulates phosphorylation of endothelial nitric-oxide synthase at Ser1179 by Akt-independent mechanisms: role of protein kinase A. J Biol Chem 2002;277:3388-3396.
72. Karnewar S, Vasamsetti SB, Gopoju R, Kanugula AK, Ganji SK, Prabhakar S, Rangaraj N, Tupperwar N, Kumar JM, Kotamraju S. Mitochondria-targeted esculetin alleviates mitochondrial dysfunction by AMPK-mediated nitric oxide and SIRT3 regulation in endothelial cells: potential implications in atherosclerosis. Sci Rep 2016;6:24108.
73. Han F, Zhang S, Hou N, Wang D, Sun X. Irisin improves endothelial function in obese mice through the AMPK-eNOS pathway. Am J Physiol Heart Circ Physiol 2015;309:H1501-H1508.
74. Ouchi N, Kobayashi H, Kihara S, Kumada M, Sato K, Inoue T, Funahashi T, Walsh K. Adiponectin stimulates angiogenesis by promoting cross-talk between AMP-activated protein kinase and Akt signaling in endothelial cells. J Biol Chem 2004;279:1304-1309.
75. Kondo M, Shibata R, Miura R, Shimano M, Kondo K, Li P, Ohashi T, Kihara S, Maeda N, Walsh K, Ouchi N, Murohara T. Caloric restriction stimulates revascularization in response to ischemia via adiponectin-mediated activation of endothelial nitric-oxide synthase. J Biol Chem 2009;284:1718-1724.
76. Kröller-Schön S, Steven S, Kossmann S, Scholz A, Daub S, Oelze M, Xia N, Hausding M, Mikhed Y, Zinssius E, Mader M, Stamm P, Treiber N, Scharffetter-Kochanek K, Li H, Schulz E, Wenzel P, Münzel T, Daiber A. Molecular mechanisms of the crosstalk between mitochondria and NADPH oxidase through reactive oxygen species-studies in white blood cells and in animal models. Antioxid Redox Signal 2014;20:247-266.
77. Dikalova AE, Bikineyeva AT, Budzyn K, Nazarewicz RR, McCann L, Lewis W, Harrison DG, Dikalov SI. Therapeutic targeting of mitochondrial superoxide in hypertension. Circ Res 2010;107:106-116.
78. Dikalov SI, Li W, Doughan AK, Blanco RR, Zafari AM. Mitochondrial reactive oxygen species and calcium uptake regulate activation of phagocytic NADPH oxidase. Am J Physiol Regul Integr Comp Physiol 2012;302:R1134-R1142.
79. Daiber A, Di Lisa F Oelze, M Kröller-Schön, S Steven, S Schulz, E Münzel, T. Crosstalk of mitochondria with NADPH oxidase via reactive oxygen and nitrogen species signalling and its role for vascular function. Br J Pharmacol 2015; doi:10.1111/bph.13403.
80. Daiber A. Redox signaling (cross-talk) from and to mitochondria involves mitochon-drial pores and reactive oxygen species. Biochim Biophys Acta-Bioenerg 2010;1797:897-906.
81. Loot AE, Schreiber JG, Fisslthaler B, Fleming I. Angiotensin II impairs endothelial function via tyrosine phosphorylation of the endothelial nitric oxide synthase. J Exp Med 2009;206:2889-2896.
82. Matsui A, Okigaki M, Amano K, Adachi Y, Jin D, Takai S, Yamashita T, Kawashima S, Kurihara T, Miyazaki M, Tateishi K, Matsunaga S, Katsume A, Honshou S, Takahashi T, Matoba S, Kusaba T, Tatsumi T, Matsubara H. Central role of calcium-dependent tyrosine kinase PYK2 in endothelial nitric oxide synthase-mediated angiogenic response and vascular function. Circulation 2007;116:1041-1051.