Peroxisome Proliferator-Activated Receptor δ Agonist, HPP593, Prevents Renal Necrosis under Chronic Ischemia

PLoS ONE

Volumn 8, Issue 5, 2013, Pages

  Fedorova, Larisa V ^a   Sodhi, Komal ^a,b   Gatto Weis, Cara ^a   Puri, Nitin ^a   Hinds, Terry D ^a   Shapiro, Joseph I ^a,b   Malhotra, Deepak ^a  

^a MEDICAL COLLEGE OF OHIO   (United States)

^b MARSHALL UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AUTOPHAGY PROTEIN 5; BECLIN 1; CYTOCHROME C; CYTOCHROME C4; HPP 593; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; MEDIUM CHAIN ACYL COENZYME A DEHYDROGENASE; MICROTUBULE ASSOCIATED PROTEIN; MICROTUBULE ASSOCIATED PROTEIN LIGHT CHAIN 3; MITOCHONDRIAL TRANSCRIPTION FACTOR A; PARKIN; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA AGONIST; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA COACTIVATOR 1ALPHA; PROTEIN BNIP3; PROTEIN P62; TRANSCRIPTION FACTOR NRF1; TRANSCRIPTION FACTOR NRF2; UNCLASSIFIED DRUG; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR DELTA; PRIMER DNA;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; KIDNEY FIBROSIS; KIDNEY ISCHEMIA; KIDNEY NECROSIS; MALE; MITOCHONDRION; NONHUMAN; OXIDATIVE STRESS; RAT; RENAL PROTECTION; UPREGULATION; AGONISTS; ANIMAL; CHRONIC DISEASE; ISCHEMIA; KIDNEY; NECROSIS; NUCLEOTIDE SEQUENCE; PATHOLOGY; SPRAGUE DAWLEY RAT; VASCULARIZATION;

ANIMALS; BASE SEQUENCE; CHRONIC DISEASE; DNA PRIMERS; ISCHEMIA; KIDNEY; MALE; NECROSIS; PPAR DELTA; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84877743633     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0064436     Document Type: Article

References (104)

1. Shanley PF, (1996) The pathology of chronic renal ischemia. Semin Nephrol 16: 21-32.
2. Cantin M, Solymoss B, Benchimol S, Desormeaux Y, Langlais J, et al. (1979) Metaplastic and mitotic activity of the ischemic (endocrine) kidney in experimental renal hypertension. Am J Pathol 96: 545-566.
3. Lerman LO, Nath KA, Rodriguez-Porcel M, Krier JD, Schwartz RS, et al. (2001) Increased oxidative stress in experimental renovascular hypertension. Hypertension 37: 541-546.
4. Lerman LO, Textor SC, Grande JP, (2009) Mechanisms of tissue injury in renal artery stenosis: ischemia and beyond. Prog Cardiovasc Dis 52: 196-203.
5. Galvez AS, Brunskill EW, Marreez Y, Benner BJ, Regula KM, et al. (2006) Distinct pathways regulate proapoptotic Nix and BNip3 in cardiac stress. J Biol Chem 281: 1442-1448.
6. Zhang J, Ney PA, (2009) Role of BNIP3 and NIX in cell death, autophagy, and mitophagy. Cell Death Differ 16: 939-946.
7. Zhang J, Ney PA, (2011) Mechanisms and Biology of B-Cell Leukemia/Lymphoma 2/Adenovirus E1B Interacting Protein 3 and Nip-Like Protein X. Antioxidants & Redox Signaling. 14: 1959-1969.
8. Dorn GW, 2nd (2010) Mitochondrial pruning by Nix and BNip3: an essential function for cardiac-expressed death factors. J Cardiovasc Transl Res 3: 374-383.
9. Gustafsson AB, Gottlieb RA, (2007) Bcl-2 family members and apoptosis, taken to heart. Am J Physiol Cell Physiol 292: C45-51.
10. Metukuri MR, Beer-Stolz D, Namas RA, Dhupar R, Torres A, et al. (2009) Expression and subcellular localization of BNIP3 in hypoxic hepatocytes and liver stress. Am J Physiol Gastrointest Liver Physiol 296: G499-509.
11. Diwan A, Krenz M, Syed FM, Wansapura J, Ren X, et al. (2007) Inhibition of ischemic cardiomyocyte apoptosis through targeted ablation of Bnip3 restrains postinfarction remodeling in mice. J Clin Invest 117: 2825-2833.
12. Althaus J, Bernaudin M, Petit E, Toutain J, Touzani O, et al. (2006) Expression of the gene encoding the pro-apoptotic BNIP3 protein and stimulation of hypoxia-inducible factor-1 alpha (HIF-1 alpha) protein following focal cerebral ischernia in rats. Neurochemistry International 48: 687-695.
13. Zhang Z, Yang X, Zhang S, Ma X, Kong J, (2007) BNIP3 upregulation and EndoG translocation in delayed neuronal death in stroke and in hypoxia. Stroke 38: 1606-1613.
14. Bruick RK, (2000) Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc Natl Acad Sci U S A 97: 9082-9087.
15. Kubasiak LA, Hernandez OM, Bishopric NH, Webster KA, (2002) Hypoxia and acidosis activate cardiac myocyte death through the Bcl-2 family protein BNIP3. Proc Natl Acad Sci U S A 99: 12825-12830.
16. Frazier DP, Wilson A, Graham RM, Thompson JW, Bishopric NH, et al. (2006) Acidosis regulates the stability, hydrophobicity, and activity of the BH3-only protein Bnip3. Antioxid Redox Signal 8: 1625-1634.
17. Kubli DA, Quinsay MN, Huang C, Lee Y, Gustafsson AB, (2008) Bnip3 functions as a mitochondrial sensor of oxidative stress during myocardial ischemia and reperfusion. Am J Physiol Heart Circ Physiol 295: H2025-2031.
18. Chen G, Ray R, Dubik D, Shi L, Cizeau J, et al. (1997) The E1B 19K/Bcl-2-binding protein Nip3 is a dimeric mitochondrial protein that activates apoptosis. J Exp Med 186: 1975-1983.
19. Vande Velde C, Cizeau J, Dubik D, Alimonti J, Brown T, et al. (2000) BNIP3 and genetic control of necrosis-like cell death through the mitochondrial permeability transition pore. Mol Cell Biol 20: 5454-5468.
20. Hamacher-Brady A, Brady NR, Logue SE, Sayen MR, Jinno M, et al. (2007) Response to myocardial ischemia/reperfusion injury involves Bnip3 and autophagy. Cell Death Differ 14: 146-157.
21. Kubli DA, Ycaza JE, Gustafsson AB, (2007) Bnip3 mediates mitochondrial dysfunction and cell death through Bax and Bak. Biochem J 405: 407-415.
22. Regula KM, Ens K, Kirshenbaum LA, (2002) Inducible expression of BNIP3 provokes mitochondrial defects and hypoxia-mediated cell death of ventricular myocytes. Circ Res 91: 226-231.
23. Quinsay MN, Lee Y, Rikka S, Sayen MR, Molkentin JD, et al. (2010) Bnip3 mediates permeabilization of mitochondria and release of cytochrome c via a novel mechanism. J Mol Cell Cardiol 48: 1146-1156.
24. Rikka S, Quinsay MN, Thomas RL, Kubli DA, Zhang X, et al. (2011) Bnip3 impairs mitochondrial bioenergetics and stimulates mitochondrial turnover. Cell Death Differ 18: 721-731.
25. Bellot G, Garcia-Medina R, Gounon P, Chiche J, Roux D, et al. (2009) Hypoxia-induced autophagy is mediated through hypoxia-inducible factor induction of BNIP3 and BNIP3L via their BH3 domains. Mol Cell Biol 29: 2570-2581.
26. Zhang H, Bosch-Marce M, Shimoda LA, Tan YS, Baek JH, et al. (2008) Mitochondrial autophagy is an HIF-1-dependent adaptive metabolic response to hypoxia. J Biol Chem 283: 10892-10903.
27. Nakamura Y, Kitamura N, Shinogi D, Yoshida M, Goda O, et al. (2012) BNIP3 and NIX mediate Mieap-induced accumulation of lysosomal proteins within mitochondria. PLoS One 7: e30767.
28. Fogo AB, (2011) PPARgamma and chronic kidney disease. Pediatr Nephrol 26: 347-351.
29. Thomas MC, Jandeleit-Dahm KA, Tikellis C, (2012) The renoprotective actions of peroxisome proliferator-activated receptors agonists in diabetes. PPAR Res 2012: 456529.
30. Sivarajah A, Chatterjee PK, Patel NS, Todorovic Z, Hattori Y, et al. (2003) Agonists of peroxisome-proliferator activated receptor-gamma reduce renal ischemia/reperfusion injury. Am J Nephrol 23: 267-276.
31. Li S, Nagothu KK, Desai V, Lee T, Branham W, et al. (2009) Transgenic expression of proximal tubule peroxisome proliferator-activated receptor-alpha in mice confers protection during acute kidney injury. Kidney Int 76: 1049-1062.
32. Chen HH, Chen TW, Lin H, (2009) Prostacyclin-induced peroxisome proliferator-activated receptor-alpha translocation attenuates NF-kappaB and TNF-alpha activation after renal ischemia-reperfusion injury. Am J Physiol Renal Physiol 297: F1109-1118.
33. Patel NS, di Paola R, Mazzon E, Britti D, Thiemermann C, et al. (2009) Peroxisome proliferator-activated receptor-alpha contributes to the resolution of inflammation after renal ischemia/reperfusion injury. J Pharmacol Exp Ther 328: 635-643.
34. Boor P, Celec P, Martin IV, Villa L, Hodosy J, et al. (2011) The peroxisome proliferator-activated receptor-alpha agonist, BAY PP1, attenuates renal fibrosis in rats. Kidney Int 80: 1182-1197.
35. Letavernier E, Perez J, Joye E, Bellocq A, Fouqueray B, et al. (2005) Peroxisome proliferator-activated receptor beta/delta exerts a strong protection from ischemic acute renal failure. J Am Soc Nephrol 16: 2395-2402.
36. Collino M, Benetti E, Miglio G, Castiglia S, Rosa AC, et al. (2011) Peroxisome proliferator-activated receptor beta/delta agonism protects the kidney against ischemia/reperfusion injury in diabetic rats. Free Radic Biol Med 50: 345-353.
37. Kennedy DJ, Vetteth S, Periyasamy SM, Kanj M, Fedorova L, et al. (2006) Central role for the cardiotonic steroid marinobufagenin in the pathogenesis of experimental uremic cardiomyopathy. Hypertension 47: 488-495.
38. Fedorova LV, Raju V, El-Okdi N, Shidyak A, Kennedy DJ, et al. (2009) The cardiotonic steroid hormone marinobufagenin induces renal fibrosis: implication of epithelial-to-mesenchymal transition. Am J Physiol Renal Physiol 296: F922-934.
39. Fedorova L, Gatto-Weis C, Smaili S, Khurshid N, Shapiro JI, et al. (2012) Down-regulation of the transcription factor snail in the placentas of patients with preeclampsia and in a rat model of preeclampsia. Reprod Biol Endocrinol 10: 15.
40. Camadro JM, Abraham NG, Levere RD, (1985) Kinetic properties of the membrane-bound human liver mitochondrial protoporphyrinogen oxidase. Arch Biochem Biophys 242: 206-212.
41. Willey JC, Crawford EL, Knight CR, Warner KA, Motten CA, et al. (2004) Standardized RT-PCR and the standardized expression measurement center. Methods Mol Biol 258: 13-41.
42. Nadasdy T, Laszik Z, Blick KE, Johnson DL, Silva FG, (1994) Tubular atrophy in the end-stage kidney: a lectin and immunohistochemical study. Hum Pathol 25: 22-28.
43. Benigni A, Morigi M, Remuzzi G, (2010) Kidney regeneration. Lancet 375: 1310-1317.
44. Niture SK, Kaspar JW, Shen J, Jaiswal AK, (2010) Nrf2 signaling and cell survival. Toxicol Appl Pharmacol 244: 37-42.
45. Sinha S, Levine B, (2008) The autophagy effector Beclin 1: a novel BH3-only protein. Oncogene 27Suppl 1: S137-148.
46. Ravikumar B, Sarkar S, Davies JE, Futter M, Garcia-Arencibia M, et al. (2010) Regulation of mammalian autophagy in physiology and pathophysiology. Physiol Rev 90: 1383-1435.
47. Ichimura Y, Kirisako T, Takao T, Satomi Y, Shimonishi Y, et al. (2000) A ubiquitin-like system mediates protein lipidation. Nature 408: 488-492.
48. Geisler S, Holmstrom KM, Skujat D, Fiesel FC, Rothfuss OC, et al. (2010) PINK1/Parkin-mediated mitophagy is dependent on VDAC1 and p62/SQSTM1. Nat Cell Biol 12: 119-131.
49. Lee M, Shin J, (2011) Triage of oxidation-prone proteins by Sqstm1/p62 within the mitochondria. Biochem Biophys Res Commun 413: 122-127.
50. Pfaller W, Rittinger M, (1980) Quantitative morphology of the rat kidney. Int J Biochem 12: 17-22.
51. Burton TR, Gibson SB, (2009) The role of Bcl-2 family member BNIP3 in cell death and disease: NIPping at the heels of cell death. Cell Death Differ 16: 515-523.
52. Gustafsson AB, (2011) Bnip3 as a dual regulator of mitochondrial turnover and cell death in the myocardium. Pediatr Cardiol 32: 267-274.
53. Lesnefsky EJ, Moghaddas S, Tandler B, Kerner J, Hoppel CL, (2001) Mitochondrial dysfunction in cardiac disease: ischemia-reperfusion, aging, and heart failure. J Mol Cell Cardiol 33: 1065-1089.
54. Dennis SC, Gevers W, Opie LH, (1991) Protons in ischemia: where do they come from; where do they go to? J Mol Cell Cardiol 23: 1077-1086.
55. Chen G, Cizeau J, Vande Velde C, Park JH, Bozek G, et al. (1999) Nix and Nip3 form a subfamily of pro-apoptotic mitochondrial proteins. J Biol Chem 274: 7-10.
56. Bonventre JV, Yang L, (2011) Cellular pathophysiology of ischemic acute kidney injury. J Clin Invest 121: 4210-4221.
57. Brezis M, Rosen S, (1995) Hypoxia of the renal medulla-its implications for disease. N Engl J Med 332: 647-655.
58. Ong SB, Gustafsson AB, (2012) New roles for mitochondria in cell death in the reperfused myocardium. Cardiovasc Res 94: 190-196.
59. Brigelius-Flohe R, Flohe L, (2011) Basic principles and emerging concepts in the redox control of transcription factors. Antioxid Redox Signal 15: 2335-2381.
60. Scarpulla RC, (2006) Nuclear control of respiratory gene expression in mammalian cells. J Cell Biochem 97: 673-683.
61. Azad MB, Chen Y, Henson ES, Cizeau J, McMillan-Ward E, et al. (2008) Hypoxia induces autophagic cell death in apoptosis-competent cells through a mechanism involving BNIP3. Autophagy 4: 195-204.
62. Kanzawa T, Zhang L, Xiao L, Germano IM, Kondo Y, et al. (2005) Arsenic trioxide induces autophagic cell death in malignant glioma cells by upregulation of mitochondrial cell death protein BNIP3. Oncogene 24: 980-991.
63. Mazure NM, Pouyssegur J, (2009) Atypical BH3-domains of BNIP3 and BNIP3L lead to autophagy in hypoxia. Autophagy 5: 868-869.
64. Kume S, Uzu T, Horiike K, Chin-Kanasaki M, Isshiki K, et al. (2010) Calorie restriction enhances cell adaptation to hypoxia through Sirt1-dependent mitochondrial autophagy in mouse aged kidney. J Clin Invest 120: 1043-1055.
65. Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, et al. (2006) Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 8: 1124-1132.
66. Herzog C, Yang C, Holmes A, Kaushal GP, (2012) zVAD-fmk prevents cisplatin-induced cleavage of autophagy proteins but impairs autophagic flux and worsens renal function. Am J Physiol Renal Physiol 303: F1239-1250.
67. Liu S, Hartleben B, Kretz O, Wiech T, Igarashi P, et al. (2012) Autophagy plays a critical role in kidney tubule maintenance, aging and ischemia-reperfusion injury. Autophagy 8.
68. Kimura T, Takabatake Y, Takahashi A, Kaimori JY, Matsui I, et al. (2011) Autophagy Protects the Proximal Tubule from Degeneration and Acute Ischemic Injury. J Am Soc Nephrol.
69. Bjorkoy G, Lamark T, Brech A, Outzen H, Perander M, et al. (2005) p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death. J Cell Biol 171: 603-614.
70. Fan W, Tang Z, Chen D, Moughon D, Ding X, et al. (2010) Keap1 facilitates p62-mediated ubiquitin aggregate clearance via autophagy. Autophagy 6.
71. Moscat J, Diaz-Meco MT, (2011) Feedback on fat: p62-mTORC1-autophagy connections. Cell 147: 724-727.
72. Nezis IP, Stenmark H (2012) p62 at the Interface of Autophagy, Oxidative Stress Signaling, and Cancer. Antioxid Redox Signal.
73. Copple IM, Lister A, Obeng AD, Kitteringham NR, Jenkins RE, et al. (2010) Physical and functional interaction of sequestosome 1 with Keap1 regulates the Keap1-Nrf2 cell defense pathway. J Biol Chem 285: 16782-16788.
74. Jain A, Lamark T, Sjottem E, Larsen KB, Awuh JA, et al. (2010) p62/SQSTM1 is a target gene for transcription factor NRF2 and creates a positive feedback loop by inducing antioxidant response element-driven gene transcription. J Biol Chem 285: 22576-22591.
75. Komatsu M, Kurokawa H, Waguri S, Taguchi K, Kobayashi A, et al. (2010) The selective autophagy substrate p62 activates the stress responsive transcription factor Nrf2 through inactivation of Keap1. Nat Cell Biol 12: 213-223.
76. Lau A, Wang XJ, Zhao F, Villeneuve NF, Wu T, et al. (2010) A noncanonical mechanism of Nrf2 activation by autophagy deficiency: direct interaction between Keap1 and p62. Mol Cell Biol 30: 3275-3285.
77. Moraes CT, (2001) What regulates mitochondrial DNA copy number in animal cells? Trends Genet 17: 199-205.
78. Clay Montier LL, Deng JJ, Bai Y, (2009) Number matters: control of mammalian mitochondrial DNA copy number. J Genet Genomics 36: 125-131.
79. Wang YX, Zhang CL, Yu RT, Cho HK, Nelson MC, et al. (2004) Regulation of muscle fiber type and running endurance by PPARdelta. PLoS Biol 2: e294.
80. Schuler M, Ali F, Chambon C, Duteil D, Bornert JM, et al. (2006) PGC1alpha expression is controlled in skeletal muscles by PPARbeta, whose ablation results in fiber-type switching, obesity, and type 2 diabetes. Cell Metab 4: 407-414.
81. Wang P, Liu J, Li Y, Wu S, Luo J, et al. (2010) Peroxisome proliferator-activated receptor {delta} is an essential transcriptional regulator for mitochondrial protection and biogenesis in adult heart. Circ Res 106: 911-919.
82. Liu J, Wang P, Luo J, Huang Y, He L, et al. (2011) Peroxisome proliferator-activated receptor beta/delta activation in adult hearts facilitates mitochondrial function and cardiac performance under pressure-overload condition. Hypertension 57: 223-230.
83. Gamboa JL, Andrade FH, (2010) Mitochondrial content and distribution changes specific to mouse diaphragm after chronic normobaric hypoxia. Am J Physiol Regul Integr Comp Physiol 298: R575-583.
84. Moraes LA, Piqueras L, Bishop-Bailey D, (2006) Peroxisome proliferator-activated receptors and inflammation. Pharmacol Ther 110: 371-385.
85. Bishop-Bailey D, Bystrom J, (2009) Emerging roles of peroxisome proliferator-activated receptor-beta/delta in inflammation. Pharmacol Ther 124: 141-150.
86. Pialat JB, Cho TH, Beuf O, Joye E, Moucharrafie S, et al. (2007) MRI monitoring of focal cerebral ischemia in peroxisome proliferator-activated receptor (PPAR)-deficient mice. NMR Biomed 20: 335-342.
87. Yin KJ, Deng Z, Hamblin M, Zhang J, Chen YE, (2011) Vascular PPARdelta protects against stroke-induced brain injury. Arterioscler Thromb Vasc Biol 31: 574-581.
88. Iwashita A, Muramatsu Y, Yamazaki T, Muramoto M, Kita Y, et al. (2007) Neuroprotective efficacy of the peroxisome proliferator-activated receptor delta-selective agonists in vitro and in vivo. J Pharmacol Exp Ther 320: 1087-1096.
89. Arsenijevic D, de Bilbao F, Plamondon J, Paradis E, Vallet P, et al. (2006) Increased infarct size and lack of hyperphagic response after focal cerebral ischemia in peroxisome proliferator-activated receptor beta-deficient mice. J Cereb Blood Flow Metab 26: 433-445.
90. Pesant M, Sueur S, Dutartre P, Tallandier M, Grimaldi PA, et al. (2006) Peroxisome proliferator-activated receptor delta (PPARdelta) activation protects H9c2 cardiomyoblasts from oxidative stress-induced apoptosis. Cardiovasc Res 69: 440-449.
91. Kapoor A, Collino M, Castiglia S, Fantozzi R, Thiemermann C, (2010) Activation of peroxisome proliferator-activated receptor-beta/delta attenuates myocardial ischemia/reperfusion injury in the rat. Shock 34: 117-124.
92. Glatz T, Stock I, Nguyen-Ngoc M, Gohlke P, Herdegen T, et al. (2010) Peroxisome-proliferator-activated receptors gamma and peroxisome-proliferator-activated receptors beta/delta and the regulation of interleukin 1 receptor antagonist expression by pioglitazone in ischaemic brain. J Hypertens 28: 1488-1497.
93. Planavila A, Rodriguez-Calvo R, Jove M, Michalik L, Wahli W, et al. (2005) Peroxisome proliferator-activated receptor beta/delta activation inhibits hypertrophy in neonatal rat cardiomyocytes. Cardiovasc Res 65: 832-841.
94. Lee CH, Chawla A, Urbiztondo N, Liao D, Boisvert WA, et al. (2003) Transcriptional repression of atherogenic inflammation: modulation by PPARdelta. Science 302: 453-457.
95. Takata Y, Liu J, Yin F, Collins AR, Lyon CJ, et al. (2008) PPARdelta-mediated antiinflammatory mechanisms inhibit angiotensin II-accelerated atherosclerosis. Proc Natl Acad Sci U S A 105: 4277-4282.
96. Altieri P, Spallarossa P, Barisione C, Garibaldi S, Garuti A, et al. (2012) Inhibition of doxorubicin-induced senescence by PPARdelta activation agonists in cardiac muscle cells: cooperation between PPARdelta and Bcl6. PLoS One 7: e46126.
97. Kurosu T, Fukuda T, Miki T, Miura O, (2003) BCL6 overexpression prevents increase in reactive oxygen species and inhibits apoptosis induced by chemotherapeutic reagents in B-cell lymphoma cells. Oncogene 22: 4459-4468.
98. Regula KM, Baetz D, Kirshenbaum LA, (2004) Nuclear factor-kappaB represses hypoxia-induced mitochondrial defects and cell death of ventricular myocytes. Circulation 110: 3795-3802.
99. Baetz D, Regula KM, Ens K, Shaw J, Kothari S, et al. (2005) Nuclear factor-kappaB-mediated cell survival involves transcriptional silencing of the mitochondrial death gene BNIP3 in ventricular myocytes. Circulation 112: 3777-3785.
100. Bishop-Bailey D, (2011) PPARs and angiogenesis. Biochem Soc Trans 39: 1601-1605.
101. Meissner M, Hrgovic I, Doll M, Kaufmann R, (2011) PPARdelta agonists suppress angiogenesis in a VEGFR2-dependent manner. Arch Dermatol Res 303: 41-47.
102. Bishop-Bailey D, (2008) A Role for PPARbeta/delta in Ocular Angiogenesis. PPAR Res 2008: 825970.
103. Sanchez-Lopez E, Lopez AF, Esteban V, Yague S, Egido J, et al. (2005) Angiotensin II regulates vascular endothelial growth factor via hypoxia-inducible factor-1alpha induction and redox mechanisms in the kidney. Antioxid Redox Signal 7: 1275-1284.
104. Tanaka T, Nangaku M (2013) Angiogenesis and hypoxia in the kidney. Nat Rev Nephrol.