Therapeutic Effects of PPAR α on Neuronal Death and Microvascular Impairment

PPAR Research

Volumn 2015, Issue , 2015, Pages

  Moran, Elizabeth P ^a   Ma, Jian Xing ^a,b  

^a UNIVERSITY OF OKLAHOMA COLLEGE OF MEDICINE   (United States)

^b UNIVERSITY OF OKLAHOMA HEALTH SCIENCES CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR ALPHA AGONIST; TRANSCRIPTION FACTOR;

ALZHEIMER DISEASE; ANTIINFLAMMATORY ACTIVITY; ANTIOXIDANT ACTIVITY; BRAIN ISCHEMIA; CARDIOVASCULAR FUNCTION; CELL DEATH; DEGENERATIVE DISEASE; DIABETIC MICROANGIOPATHY; DIABETIC RETINOPATHY; DRUG MECHANISM; ENDOTHELIAL DYSFUNCTION; ENERGY METABOLISM; GENE TARGETING; HUMAN; INFLAMMATION; MICROANGIOPATHY; NEOVASCULARIZATION (PATHOLOGY); NERVE CELL; NEUROPROTECTION; NON INSULIN DEPENDENT DIABETES MELLITUS; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PERIPHERAL NEUROPATHY; PROMOTER REGION; RETINOPATHY; REVIEW; SPINAL CORD INJURY; THERAPY EFFECT; TRANSCRIPTION REGULATION; TRAUMATIC BRAIN INJURY;

EID: 84937149422     PISSN: 16874757     EISSN: 16874765     Source Type: Journal    
DOI: 10.1155/2015/595426     Document Type: Review

References (108)

1. J. Wu, L. Chen, D. Zhang et al., "Peroxisome proliferatoractivated receptors and renal diseases, " Frontiers in Bioscience, vol. 14, no. 3, pp. 995-1009, 2009.
2. A. Hiukka, M. Maranghi, N. Matikainen, and M.-R. Taskinen, "PPAR: an emerging therapeutic target in diabetic microvascular damage, " Nature Reviews Endocrinology, vol. 6, no. 8, pp. 454-463, 2010.
3. P. Lefebvre, G. Chinetti, J. C. Fruchart, and B. Staels, "Sorting out the roles of PPAR in energy metabolism and vascular homeostasis, " The Journal of Clinical Investigation, vol. 116, no. 3, pp. 571-580, 2006.
4. R. Bordet, T. Ouk, O. Petrault et al., "PPAR: a newpharmacological target for neuroprotection in stroke and neurodegenerative diseases, " Biochemical Society Transactions, vol. 34, no. 6, pp. 1341-1346, 2006.
5. L. Chen and G. Yang, "PPARs integrate the mammalian clock and energy metabolism, " PPAR Research, vol. 2014, Article ID 653017, 6 pages, 2014.
6. A. Y. Y. Cheng and L. A. Leiter, "PPAR-alpha: therapeutic role in diabetes-related cardiovascular disease, " Diabetes, Obesity and Metabolism, vol. 10, no. 9, pp. 691-698, 2008.
7. A. Papi, T. Guarnieri, G. Storci et al., "Nuclear receptors agonists exert opposing effects on the inflammation dependent survival of breast cancer stem cells, " Cell Death and Differentiation, vol. 19, no. 7, pp. 1208-1219, 2012.
8. J. K. Barbiero, R. Santiago, F. S. Tonin et al., "PPAR-alpha agonist fenofibrate protects against the damaging effects of MPTP in a rat model of Parkinson's disease, " Progress in Neuro-Psychopharmacology and Biological Psychiatry, vol. 53, pp. 35-44, 2014.
9. D. Deplanque, P. Gelé, O. Pétrault et al., "Peroxisome proliferator-activated receptor activation as a mechanism of preventive neuroprotection induced by chronic fenofibrate treatment, " The Journal of Neuroscience, vol. 23, no. 15, pp. 6264-6271, 2003.
10. C. K. Combs, P. Bates, J. C. Karlo, and G. E. Landreth, "Regulation of beta-amyloid stimulated proinflammatory responses by peroxisome proliferator-activated receptor alpha, " Neurochemistry International, vol. 39, no. 5-6, pp. 449-457, 2001.
11. K. Rajamani, P. G. Colman, L. P. Li et al., "Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial, " The Lancet, vol. 373, no. 9677, pp. 1780-1788, 2009.
12. E. Moran, L. Ding, Z. Wang et al., "Protective and antioxidant effects of PPARalpha in the ischemic retina, " Investigative Ophthalmology & Visual Science, vol. 55, no. 7, pp. 4568-4576, 2014.
13. L. Ding, R. Cheng, Y. Hu et al., "Peroxisome proliferatoractivated receptor protects capillary pericytes in the retina, " The American Journal of Pathology, vol. 184, no. 10, pp. 2709-2720, 2014.
14. L. G. Cervantes-Pérez, M. de La Luz Ibarra-Lara, B. Escalante et al., "Endothelial nitric oxide synthase impairment is restored by clofibrate treatment in an animal model of hypertension, " European Journal of Pharmacology, vol. 685, no. 1-3, pp. 108-115, 2012.
15. Y. Hu, Y. Chen, L. Ding et al., "Pathogenic role of diabetesinduced PPAR down-regulation in microvascular dysfunction, " Proceedings of the National Academy of Sciences of the United States of America, vol. 110, no. 38, pp. 15401-15406, 2013.
16. M.-C. Mong and M.-C. Yin, "Nuclear factor b-dependent antiinflammatory effects of s-allyl cysteine and s-propyl cysteine in kidney of diabetic mice, " Journal of Agricultural and Food Chemistry, vol. 60, no. 12, pp. 3158-3165, 2012.
17. A. Keech, R. J. Simes, P. Barter et al., "Effects of long-termfenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial, " The Lancet, vol. 366, no. 9500, pp. 1849-1861, 2005.
18. F. Ismail-Beigi, T. Craven, M. A. Banerji et al., "Effect of intensive treatment of hyperglycaemia on microvascular outcomes in type 2 diabetes: an analysis of the ACCORD randomised trial, " The Lancet, vol. 376, no. 9739, pp. 419-430, 2010.
19. T. Ouk, S. Gautier, M. Pétrault et al., "Effects of the PPAR agonist fenofibrate on acute and short-term consequences of brain ischemia, " Journal of Cerebral Blood Flow andMetabolism, vol. 34, no. 3, pp. 542-551, 2014.
20. M. Collino, M. Aragno, R. Mastrocola et al., "Oxidative stress and inflammatory response evoked by transient cerebral ischemia/reperfusion: effects of the PPAR-alpha agonist WY14643, " Free Radical Biology & Medicine, vol. 41, no. 4, pp. 579-589, 2006.
21. T. Genovese, E. Mazzon, R. Di Paola et al., "Role of endogenous ligands for the peroxisome proliferators activated receptors alpha in the secondary damage in experimental spinal cord trauma, " Experimental Neurology, vol. 194, no. 1, pp. 267-278, 2005.
22. V. C. Besson, X. R. Chen, M. Plotkine, and C. Marchand-Verrecchia, "Fenofibrate, a peroxisome proliferator-activated receptor agonist, exerts neuroprotective effects in traumatic brain injury, " Neuroscience Letters, vol. 388, no. 1, pp. 7-12, 2005.
23. X. R. Chen, V. C. Besson, T. Beziaud, M. Plotkine, and C. Marchand-Leroux, "Combination therapy with fenofibrate, a peroxisome proliferator-activated receptor agonist, and simvastatin, a 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor, on experimental traumatic brain injury, " Journal of Pharmacology and ExperimentalTherapeutics, vol. 326, no. 3, pp. 966-974, 2008.
24. X. R. Chen, V. C. Besson, B. Palmier, Y. Garcia, M. Plotkine, and C. Marchand-Leroux, "Neurological recovery-promoting, antiinflammatory, and anti-oxidative effects afforded by fenofibrate, a PPAR alpha agonist, in traumatic brain injury, " Journal of Neurotrauma, vol. 24, no. 7, pp. 1119-1131, 2007.
25. L. Khalaj, S. Chavoshi Nejad, M. Mohammadi et al., "Gemfibrozil pretreatment proved protection against acute restraint stress-induced changes in the male rats' hippocampus, " Brain Research, vol. 1527, pp. 117-130, 2013.
26. E. Esposito, D. Impellizzeri, E. Mazzon, I. Paterniti, and S. Cuzzocrea, "Neuroprotective activities of palmitoylethanolamide in an animal model of Parkinson's disease, " PLoS ONE, vol. 7, no. 8, Article ID e41880, 2012.
27. D. Uppalapati, N. R. Das, R. P. Gangwal, M. V. Damre, A. T. Sangamwar, and S. S. Sharma, "Neuroprotective potential of peroxisome proliferator activated receptor- agonist in cognitive impairment in Parkinson's disease: behavioral, biochemical, and PBPK profile, " PPAR Research, vol. 2014, Article ID 753587, 9 pages, 2014.
28. Y. R. Cho, J. H. Lim, M. Y. Kim et al., "Therapeutic effects of fenofibrate on diabetic peripheral neuropathy by improving endothelial and neural survival in db/db mice, " PLoS ONE, vol. 9, no. 1, Article ID0083204, 2014.
29. K. Rajamani, M. Donoghoe, L. Li et al., "Abstract 18987: fenofibrate reduces peripheral neuropathy in type 2 diabetes: the fenofibrate intervention and event lowering in diabetes (FIELD) study, " Circulation, vol. 122, no. A1, p. 8997, 2010.
30. P. Bogdanov, C. Hernández, L. Corraliza, A. R. Carvalho, and R. Simó, "Effect of fenofibrate on retinal neurodegeneration in an experimental model of type 2 diabetes, " Acta Diabetologica, 2014.
31. G. Desideri, G. Croce, M. Tucci et al., "Effects of bezafibrate and simvastatin on endothelial activation and lipid peroxidation in hypercholesterolemia: evidence of different vascular protection by different lipid-lowering treatments, " The Journal of Clinical Endocrinology and Metabolism, vol. 88, no. 11, pp. 5341-5347, 2003.
32. D. A. Playford, G. F. Watts, J. D. Best, and V. Burke, "Effect of fenofibrate on brachial artery flow-mediated dilatation in type 2 diabetesmellitus, " American Journal of Cardiology, vol. 90, no. 11, pp. 1254-1257, 2002.
33. D. A. Playford, G. F. Watts, K. D. Croft, andV. Burke, "Combined effect of coenzyme Q10 and fenofibrate on forearm microcirculatory function in type 2 diabetes, " Atherosclerosis, vol. 168, no. 1, pp. 169-179, 2003.
34. M. Evans, R. A. Anderson, J. Graham et al., "Ciprofibrate therapy improves endothelial function and reduces postprandial lipemia and oxidative stress in type 2 diabetes mellitus, " Circulation, vol. 101, no. 15, pp. 1773-1779, 2000.
35. Y. Chen, Y. Hu, M. Lin et al., "Therapeutic effects of PPAR agonists on diabetic retinopathy in type 1 diabetes models, " Diabetes, vol. 62, no. 1, pp. 261-272, 2013.
36. Z. Wang, E. Moran, L. Ding, R. Cheng, X. Xu, and J.-X. Ma, "PPAR regulates mobilization and homing of endothelial progenitor cells through the HIF-1/SDF-1 pathway, " Investigative Ophthalmology & Visual Science, vol. 55, no. 6, pp. 3820-3832, 2014.
37. E. Mazzon, C. Crisafulli, M. Galuppo, and S. Cuzzocrea, "Role of peroxisome proliferator-activated receptor-alpha in ileum tight junction alteration in mouse model of restraint stress, " The American Journal of Physiology-Gastrointestinal and Liver Physiology, vol. 297, no. 3, pp. G488-G505, 2009.
38. J. Varet, L. Vincent, P. Mirshahi et al., "Fenofibrate inhibits angiogenesis in vitro and in vivo, " Cellular and Molecular Life Sciences, vol. 60, no. 4, pp. 810-819, 2003.
39. M. Meissner, M. Stein, C. Urbich et al., "PPARalpha activators inhibit vascular endothelial growth factor receptor-2 expression by repressing Sp1-dependent DNA binding and transactivation, " Circulation Research, vol. 94, no. 3, pp. 324-332, 2004.
40. C. Swart, W. Haylett, C. Kinnear, G. Johnson, S. Bardien, and B. Loos, "Neurodegenerative disorders: dysregulation of a carefully maintained balance?" Experimental Gerontology, vol. 58, pp. 279-291, 2014.
41. A. C. McKee, D. H. Daneshvar, V. E. Alvarez, and T. D. Stein, "The neuropathology of sport, " Acta Neuropathologica, vol. 127, no. 1, pp. 29-51, 2014.
42. S. F. Abcouwer and T. W. Gardner, "Diabetic retinopathy: loss of neuroretinal adaptation to the diabeticmetabolic environment, " Annals of the New York Academy of Sciences, vol. 1311, no. 1, pp. 174-190, 2014.
43. H. L. Ip and D. S. Liebeskind, "The future of ischemic stroke: flow from prehospital neuroprotection to definitive reperfusion, " Interventional Neurology, vol. 2, no. 3, pp. 105-117, 2014.
44. M. G. Scioli, A. Bielli, G. Arcuri, A. Ferlosio, and A. Orlandi, "Ageing and microvasculature, " Vascular Cell, vol. 6, no. 1, article 19, 2014.
45. J. Folkman, "Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis, " The New England Journal ofMedicine, vol. 333, no. 26, pp. 1757-1763, 1995.
46. G. A. Lutty, "Effects of diabetes on the eye, " InvestigativeOphthalmology and Visual Science, vol. 54, no. 14, pp. ORSF81-ORSF87, 2013.
47. W. R. Brown and C. R. Thore, "Review: cerebral microvascular pathology in ageing and neurodegeneration, " Neuropathology and Applied Neurobiology, vol. 37, no. 1, pp. 56-74, 2011.
48. D. A. Antonetti, R. Klein, and T. W. Gardner, "Diabetic retinopathy, "The New England Journal ofMedicine, vol. 366, no. 13, pp. 1227-1239, 2012.
49. B. Poljsak, D. ?Suput, and I. Milisav, "Achieving the balance between ROS and antioxidants: when to use the synthetic antioxidants, " Oxidative Medicine and Cellular Longevity, vol. 2013, Article ID 956792, 11 pages, 2013.
50. S. Chakraborty, J. Bornhorst, T. T. Nguyen, and M. Aschner, "Oxidative stress mechanisms underlying parkinson's disease associated neurodegeneration in C. elegans, " International Journal of Molecular Sciences, vol. 14, no. 11, pp. 23103-23128, 2013.
51. G. E. Lang, "Mechanisms of retinal neurodegeneration as a result of diabetes mellitus, " Klinische Monatsblatter fur Augenheilkunde, vol. 230, no. 9, pp. 929-931, 2013.
52. D. van Rossum and U.-K. Hanisch, "Microglia, " Metabolic Brain Disease, vol. 19, no. 3-4, pp. 393-411, 2004.
53. M. J. Santos, R. A. Quintanilla, A. Toro et al., "Peroxisomal proliferation protects from -amyloid neurodegeneration, " The Journal of Biological Chemistry, vol. 280, no. 49, pp. 41057-41068, 2005.
54. T. Kukar, M. P. Murphy, J. L. Eriksen et al., "Diverse compounds mimic Alzheimer disease-causing mutations by augmenting A42 production, " Nature Medicine, vol. 11, no. 5, pp. 545-550, 2005.
55. S. Brune, H. Kölsch, U. Ptok et al., "Polymorphism in the peroxisome proliferator-activated receptor gene influences the risk for Alzheimer's disease, " Journal of Neural Transmission, vol. 110, no. 9, pp. 1041-1050, 2003.
56. A. Sjölander, L. Minthon, N. Bogdanovic, A. Wallin, H. Zetterberg, and K. Blennow, "The PPAR-alpha gene in Alzheimer's disease: lack of replication of earlier association, " Neurobiology of Aging, vol. 30, no. 4, pp. 666-668, 2009.
57. O. Hwang, "Role of oxidative stress in Parkinson's disease, " Experimental Neurobiology, vol. 22, no. 1, pp. 11-17, 2013.
58. J. K. Barbiero, R. M. Santiago, D. S. Persike et al., "Neuroprotective effects of peroxisome proliferator-activated receptor alpha and gamma agonists in model of parkinsonism induced by intranigral 1-methyl-4-phenyl-1, 2, 3, 6-tetrahyropyridine, " Behavioural Brain Research, vol. 274, pp. 390-399, 2014.
59. J. Ruiz-Medina, J. A. Flores, I. Tasset, I. Tunez, O. Valverde, and E. Fernandez-Espejo, "Alteration of neuropathic and visceral pain in female C57BL/6J mice lacking the PPAR gene, " Psychopharmacology, vol. 222, no. 3, pp. 477-488, 2012.
60. J. LoVerme, R. Russo, G. la Rana et al., "Rapid broad-spectrum analgesia through activation of peroxisome proliferatoractivated receptor-alpha, " Journal of Pharmacology and Experimental Therapeutics, vol. 319, no. 3, pp. 1051-1061, 2006.
61. M. Suardáz, G. Estivill-Torrús, C. Goicoechea, A. Bilbao, and F. Rodrguez de Fonseca, "Analgesic properties of oleoylethanolamide (OEA) in visceral and inflammatory pain, " Pain, vol. 133, no. 1-3, pp. 99-110, 2007.
62. N. Marx, B. Kehrle, K. Kohlhammer et al., "PPAR activators as antiinflammatory mediators in human T lymphocytes: implications for atherosclerosis and transplantation-associated arteriosclerosis, " Circulation Research, vol. 90, no. 6, pp. 703-710, 2002.
63. A. Keech, P. Mitchell, P. Summanen et al., "Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD study): a randomised controlled trial, " The Lancet, vol. 370, no. 9600, pp. 1687-1697, 2007.
64. H. N. Ginsberg, M. B. Elam, L. C. Lovato et al., "Effects of combination lipid therapy in type 2 diabetes mellitus, " New England Journal ofMedicine, vol. 362, no. 17, pp. 1563-1574, 2010.
65. P. W. M. Kleikers, K. Wingler, J. J. R. Hermans et al., "NADPH oxidases as a source of oxidative stress and molecular target in ischemia/reperfusion injury, " Journal of Molecular Medicine, vol. 90, no. 12, pp. 1391-1406, 2012.
66. E. Lyros, C. Bakogiannis, Y. Liu, and K. Fassbender, "Molecular links between endothelial dysfunction and eurodegeneration in Alzheimer's diseas, " Current Alzheimer Research, vol. 11, no. 1, pp. 18-26, 2014.
67. A. Minagar, A. H. Maghzi, J. C. Mcgee, and S. J. Alexander, "Emerging roles of endothelial cells in multiple sclerosis pathophysiology and therapy, " Neurological Research, vol. 34, no. 8, pp. 738-745, 2012.
68. A. A. F. Sima, W. Zhang, and G. Grunberger, "Type 1 diabetic neuropathy and C-peptide, " Experimental Diabesity Research, vol. 5, no. 1, pp. 65-77, 2004.
69. C. Rask-Madsen and G. L. King, "Vascular complications of diabetes: mechanisms of injury and protective factors, " Cell Metabolism, vol. 17, no. 1, pp. 20-33, 2013.
70. G. R. Drummond and C. G. Sobey, "Endothelial NADPH oxidases: which NOX to target in vascular disease?" Trends in Endocrinology & Metabolism, vol. 25, no. 9, pp. 452-463, 2014.
71. M. Fisher, "Injuries to the vascular endothelium: vascular wall and endothelial dysfunction, " Reviews in Neurological Diseases, vol. 5, supplement 1, pp. S4-S11, 2008.
72. J. T. Durham and I. M. Herman, "Microvascular modifications in diabetic retinopathy, " Current Diabetes Reports, vol. 11, no. 4, pp. 253-264, 2011.
73. N. Lois, R. V. McCarter, C. O'Neill, R. J. Medina, andA. W. Stitt, "Endothelial progenitor cells in diabetic retinopath, " Frontiers in Endocrinology, vol. 5, Article IDArticle 44, 2014.
74. J. YellowleesDouglas, A. D. Bhatwadekar, S. LiCalzi et al., "Bone marrow-CNS connections: implications in the pathogenesis of diabetic retinopathy, " Progress in Retinal and Eye Research, vol. 31, no. 5, pp. 481-494, 2012.
75. A. Jacob and J. J. Alexander, "Complement and blood-brain barrier integrity, "Molecular Immunology, vol. 61, no. 2, pp. 149-152, 2014.
76. S. J. Hamilton, G. T. Chew, and G. F. Watts, "Therapeutic regulation of endothelial dysfunction in type 2 diabetes mellitus, " Diabetes and Vascular Disease Research, vol. 4, no. 2, pp. 89-102, 2007.
77. G. Russo, J. A. Leopold, and J. Loscalzo, "Vasoactive substances: nitric oxide and endothelial dysfunction in therosclerosis, " Vascular Pharmacology, vol. 38, no. 5, pp. 259-269, 2002.
78. M. E. Widlansky, N. Gokce, J. F. Keaney Jr., and J. A. Vita, "The clinical implications of endothelial dysfunction, " Journal of the American College of Cardiology, vol. 42, no. 7, pp. 1149-1160, 2003.
79. J. Chou, S. Rollins, and A. A. Fawzi, "Role of endothelial cell and pericyte dysfunction in diabetic retinopathy: review of techniques in rodent models, " in Retinal Degenerative Diseases, vol. 801 of Advances in Experimental Medicine and Biology, pp. 669-675, Springer, New York, NY, USA, 2014.
80. A. Hiukka, J. Westerbacka, E. S. Leinonen et al., "Long-term effects of fenofibrate on carotid intima-media thickness and augmentation index in subjects with type 2 diabetes mellitus, " Journal of the American College of Cardiology, vol. 52, no. 25, pp. 2190-2197, 2008.
81. J.-C. Hogue, B. Lamarche, A. J. Tremblay, J. Bergeron, C. Gagné, and P. Couture, "Differential effect of atorvastatin and fenofibrate on plasma oxidized low-density lipoprotein, inflammation markers, and cell adhesion molecules in patients with type 2 diabetes mellitus, " Metabolism: Clinical and Experimental, vol. 57, no. 3, pp. 380-386, 2008.
82. A. Avogaro, M. Miola, A. Favaro et al., "Gemfibrozil improves insulin sensitivity and flow-mediated vasodilatation in type 2 diabetic patients, " European Journal of Clinical Investigation, vol. 31, no. 7, pp. 603-609, 2001.
83. M. E. Poynter and R. A. Daynes, "Peroxisome proliferatoractivated receptor activation modulates cellular redox status, represses nuclear factor-B signaling, and reduces inflammatory cytokine production in aging, " Journal of Biological Chemistry, vol. 273, no. 49, pp. 32833-32841, 1998.
84. P. Delerive, K. de Bosscher, S. Besnard et al., "Peroxisome proliferator-activated receptor negatively regulates the vascular inflammatory gene response by negative cross-talk with transcription factors NF-kappaB and AP-1, " The Journal of Biological Chemistry, vol. 274, no. 45, pp. 32048-32054, 1999.
85. R. Simó andC. Hernández, "Neurodegeneration in the diabetic eye: new insights and therapeutic perspectives, " Trends in Endocrinology & Metabolism, vol. 25, no. 1, pp. 23-33, 2014.
86. B. V. Zlokovic, "Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders, " Nature Reviews Neuroscience, vol. 12, no. 12, pp. 723-738, 2011.
87. M. P. Bhatt, Y.-C. Lim, and K.-S. Ha, "C-peptide replacement therapy as an emerging strategy for preventing diabetic vasculopathy, " Cardiovascular Research, vol. 104, no. 2, pp. 234-244, 2014.
88. R. Jin, G. Yang, and G. Li, "Molecular insights and therapeutic targets for blood-brain barrier disruption in ischemic stroke: critical role of matrix metalloproteinases and tissue-type plasminogen activator, " Neurobiology of Disease, vol. 38, no. 3, pp. 376-385, 2010.
89. S. F. Rimoldi, M. Yuzefpolskaya, Y. Allemann, and F. Messerli, "Flash pulmonary edema, " Progress in Cardiovascular Diseases, vol. 52, no. 3, pp. 249-259, 2009.
90. Q. Xu, T. Qaum, and A. P. Adamis, "Sensitive blood-retinal barrier breakdown quantitation using Evans blue, " Investigative Ophthalmology & Visual Science, vol. 42, no. 3, pp. 789-794, 2001.
91. T. Frey and D. A. Antonetti, "Alterations to the blood-retinal barrier in diabetes: cytokines and reactive oxygen species, " Antioxidants and Redox Signaling, vol. 15, no. 5, pp. 1271-1284, 2011.
92. W. Huang, L. Chen, B. Zhang, M. Park, and M. Toborek, "PPAR agonist-mediated protection against HIV Tat-induced cerebrovascular toxicity is enhanced inMMP-9-deficient mice, " Journal of Cerebral BloodFlowandMetabolism, vol. 34, no. 4, pp. 646-653, 2014.
93. W. Huang, Y. E. Sung, I. E. András, B. Hennig, and M. Toborek, "PPAR and PPAR attenuate HIV-induced dysregulation of tight junction proteins by modulations of matrix metalloproteinase and proteasome activities, " The FASEB Journal, vol. 23, no. 5, pp. 1596-1606, 2009.
94. C. Mysiorek, M. Culot, L. Dehouck et al., "Peroxisome proliferator-activated receptor activation protects brain capillary endothelial cells from oxygen-glucose deprivation-induced hyperpermeability in the blood-brain barrier, " Current Neurovascular Research, vol. 6, no. 3, pp. 181-193, 2009.
95. S. Takeda, N. Sato, and R. Morishita, "Systemic inflammation, blood-brain barrier vulnerability and cognitive/non-cognitive symptoms in Alzheimer disease: relevance to pathogenesis and therapy, " Frontiers in Aging Neuroscience, vol. 6, article 171, 2014.
96. H. Lee and I. S. Pienaar, "Disruption of the blood-brain barrier in parkinson's disease: curse or route to a cure?" Frontiers in Bioscience, vol. 19, no. 2, pp. 272-280, 2014.
97. S. C. Thal and W. Neuhaus, "The blood-brain barrier as a target in traumatic brain injury treatment, " Archives of Medical Research, 2014.
98. G. Tremolada, C. Del Turco, R. Lattanzio et al., "The role of angiogenesis in the development of proliferative diabetic retinopathy: impact of intravitreal anti-VEGF treatment, " Experimental Diabetes Research, vol. 2012, Article ID 728325, 8 pages, 2012.
99. K. Mittal, J. Ebos, and B. Rini, "Angiogenesis and the tumor microenvironment: vascular endothelial growth factor and beyond, " Seminars in Oncology, vol. 41, no. 2, pp. 235-251, 2014.
100. U. Sadat, F. A. Jaffer, M. A. van Zandvoort, S. J. Nicholls, D. Ribatti, and J. H. Gillard, "Inflammation and neovascularization intertwined in atherosclerosis: imagingof structural andmolecular imaging targets, " Circulation, vol. 130, no. 9, pp. 786-794, 2014.
101. A. Salam, R. Mathew, and S. Sivaprasad, "Treatment of proliferative diabetic retinopathy with anti-VEGF agents, " Acta Ophthalmologica, vol. 89, no. 5, pp. 405-411, 2011.
102. D. Cervia, E. Catalani, M. DalMonte, and G. Casini, "Vascular endothelial growth factor in the ischemic retina and its regulation by somatostatin, " Journal of Neurochemistry, vol. 120, no. 5, pp. 818-829, 2012.
103. M. N. Gao and Y. Li, "The regulation of VEGFs/VEGFRs in tumor angiogenesis byWnt/beta-catenin andNF-kappaB signal pathway, " Sheng Li Ke Xue Jin Zhan, vol. 44, no. 1, pp. 72-74, 2013.
104. S. L. Calzi, M. B. Neu, L. C. Shaw, J. L. Kielczewski, N. I. Moldovan, and M. B. Grant, "EPCs and pathological angiogenesis: when good cells go bad, " Microvascular Research, vol. 79, no. 3, pp. 207-216, 2010.
105. A. R. Vasudevan and P. H. Jones, "Effective use of combination lipid therapy, " Current Cardiology Reports, vol. 7, no. 6, pp. 471-479, 2005.
106. R.-D. Ting, A. C. Keech, P. L. Drury et al., "Benefits and safety of long-term fenofibrate therapy in people with type 2 diabetes and renal impairment: the FIELD study, " Diabetes Care, vol. 35, no. 2, pp. 218-225, 2012.
107. P. Balakumar, R. Varatharajan, Y. H. Nyo et al., "Fenofibrate and dipyridamole treatments in low-doses either alone or in combination blunted the development of nephropathy in diabetic rats, " Pharmacological Research, vol. 90, pp. 36-47, 2014.
108. Y. A. Hong, J. H. Lim, M. Y. Kim et al., "Fenofibrate improves renal lipotoxicity through activation of AMPK-PGC-1 in db/db mice, " PLoS ONE, vol. 9, no. 5, Article ID e96147, 2014.