The DOI matches its Crossref record; 47 of the 47 references it cites were found in a registry or an index.
Peroxisome Proliferator-Activated Receptor α Agonists Increase Nitric Oxide Synthase Expression in Vascular Endothelial Cells
Abstract
Objective— There has been accumulating evidence demonstrating that activators for peroxisome proliferator-activated receptor α (PPARα) have antiinflammatory, antiatherogenic, and vasodilatory effects. We hypothesized that PPARα activators can modulate endothelial nitric oxide synthase (eNOS) expression and its activity in cultured vascular endothelial cells. Methods and Results— Bovine aortic endothelial cells were treated with the PPARα activator fenofibrate. The amount of eNOS activity and the expression of eNOS protein and its mRNA were determined. Our data show that treatment with fenofibrate for 48 hours resulted in an increase in eNOS activity. Fenofibrate failed to increase eNOS activity within 1 hour. Fenofibrate also increased eNOS protein as well as its mRNA levels. RU486, which has been shown to antagonize PPARα action, inhibited the fenofibrate-induced upregulation of eNOS protein expression. WY14643 and bezafibrate also increased eNOS protein levels, whereas rosiglitazone did not. Transient transfection experiments using human eNOS promoter construct showed that fenofibrate failed to enhance eNOS promoter activity. Actinomycin D studies demonstrated that the half-life of eNOS mRNA increased with fenofibrate treatment. Conclusions— PPARα activators upregulate eNOS expression, mainly through mechanisms of stabilizing eNOS mRNA. This is a new observation to explain one of the mechanisms of PPARα-mediated cardiovascular protection.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Diep et al. [101] and Goya et al. [102] reported that FF increases endothelial Nitric Oxide (NO) availability.”
From Fenofibrate and metabolic syndrome (2010) · cites this paper as [102]
Citations
Cites
A novel potent vasoconstrictor peptide produced by vascular endothelial cells
Yanagisawa, M., Kurihara, H., Kimura, S., Tomobe, Y. I., Kobayashi, M., Mitsui, Y., Yazaki, Y., Goto, K., & Masaki, T. (1988) · Nature · doi:10.1038/332411a0 · Cited by 10,716
The L-Arginine-Nitric Oxide Pathway
Epstein, F. H., Moncada, S., & Higgs, A. (1993) · New England Journal of Medicine · doi:10.1056/nejm199312303292706 · Cited by 6,678
Activation of nitric oxide synthase in endothelial cells by Akt-dependent phosphorylation
Dimmeler, S., Fleming, I., Fisslthaler, B., Hermann, C., Busse, R., & Zeiher, A. M. (1999) · Nature · doi:10.1038/21224 · Cited by 3,591
Regulation of endothelium-derived nitric oxide production by the protein kinase Akt
Fulton, D. J., Gratton, J., McCabe, T. J. D., Fontana, J. T., Fujio, Y., Walsh, K. X., Franke, T. F., Papapetropoulos, A., & Sessa, W. C. (1999) · Nature · doi:10.1038/21218 · Cited by 2,616
Roles of PPARs in health and disease
Kersten, S., Desvergne, B., & Wahli, W. (2000) · Nature · doi:10.1038/35013000 · Cited by 1,956
Mechanism of Action of Fibrates on Lipid and Lipoprotein Metabolism
Staels, B., Dallongeville, J., Auwerx, J., Schoonjans, K., Leitersdorf, E., & Fruchart, J.-C. (1998) · Circulation · doi:10.1161/01.cir.98.19.2088 · Cited by 1,786
Caterina, R. D., Libby, P., Peng, H., Thannickal, V. J., Rajavashisth, T. B., Gimbrone, M. A., Shin, W. S., & Liao, J. K. (1995) · Journal of Clinical Investigation · doi:10.1172/jci118074 · Cited by 1,781
Joannidès, R., Haefeli, W. E., Linder, L., Richard, V. J., Bakkali, E. H., Thuillez, C., & Lüscher, T. F. (1995) · Circulation · doi:10.1161/01.cir.91.5.1314 · Cited by 1,622
Interaction of oestrogen receptor with the regulatory subunit of phosphatidylinositol-3-OH kinase
Simoncini, T., Hafezi‐Moghadam, A., Brazil, D. P., Ley, K. F., Chin, W. W., & Liao, J. K. (2000) · Nature · doi:10.1038/35035131 · Cited by 1,436
Krey, G. D., Braissant, O., L’Horset, F., Kalkhoven, E., Perroud, M., Parker, M. G., & Wahli, W. (1997) · Molecular Endocrinology · doi:10.1210/mend.11.6.0007 · Cited by 1,230
Research works printed but not linked: 10
Cited by
Sorted by citations
Items 101–174 of 174
Liu, J., Lu, C., Li, F., Wang, H., He, L., Hao, Y., Chen, A. F., An, H., Wang, X., Hong, T., et al. (2011) · PPAR Research · doi:10.1155/2011/523520 · Cited by 21
Harmer, J. A., KEECH, A. C., Veillard, A., Skilton, M. R., Marwick, T. H., Watts, G. F., Meredith, I. T., & Celermajer, D. S. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.07.038 · Cited by 21
Wang, G., He, L., Liu, J., Yu, J., Feng, X., Li, F., Hao, Y., Mao, J., Hong, T., Chen, A. F., et al. (2012) · Cardiovascular Therapeutics · doi:10.1111/j.1755-5922.2011.00307.x · Cited by 18
Sahebkar, A., Giua, R., Pedone, C., Ray, K., Vallejo-Vaz, A., & Costanzo, L. (2016) · Pharmacological Research · doi:10.1016/j.phrs.2016.06.011 · Cited by 18
Morel, J., & Singer, M. (2014) · Intensive Care Medicine Experimental · doi:10.1186/2197-425x-2-9 · Cited by 18
Yousefipour, Z., & Newaz, M. (2014) · Acta Pharmacologica Sinica · doi:10.1038/aps.2013.193 · Cited by 17
Banks, T., & Oyekan, A. (2008) · Journal of Hypertension · doi:10.1097/hjh.0b013e3282f2f0f3 · Cited by 17
Azimzadeh, O., Subramanian, V., Sievert, W., Merl‐Pham, J., Oleksenko, K., Rosemann, M., Multhoff, G., Atkinson, M. J., & Tapio, S. (2021) · Biomedicines · doi:10.3390/biomedicines9121845 · Cited by 16
Ouk, T., Potey, C., Laprais, M., Gautier, S., Hanf, R., Darteil, R., Staels, B., Duriez, P., & Bordet, R. (2013) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.12035 · Cited by 16
Peroxisome proliferator-activated receptor agonists in a battle against the aging kidney
Speeckaert, M. M., Vanfraechem, C., Speeckaert, R., & Delanghe, J. (2014) · Ageing Research Reviews · doi:10.1016/j.arr.2014.01.006 · Cited by 16
Omae, T., Nagaoka, T., Tanano, I., Kamiya, T., & Yoshida, A. (2012) · Investigative Ophthalmology & Visual Science · doi:10.1167/iovs.11-8841 · Cited by 16
Cortes-Lopez, F., Sánchez-Mendoza, A., Centurión, D., Cervantes-Pérez, L. G., Castrejón-Téllez, V., del Valle‐Mondragón, L., Soria‐Castro, E., Ramírez, V., Sánchez‐López, A., Pastelín-Hernández, G. S., et al. (2021) · PPAR Research · doi:10.1155/2021/8895376 · Cited by 16
Parishin alleviates vascular ageing in mice by upregulation of Klotho
Zhao, X., Zhou, S., Liu, Y., Gong, C., Xiang, L., Li, S., Wang, P., Wang, Y., Sun, L., Zhang, Q., et al. (2023) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.17740 · Cited by 13
Modulatory Effect of Fenofibrate on Endothelial Production of Neutrophil Chemokines IL-8 and ENA-78
Price, E. T., Welder, G. J., & Zineh, I. (2012) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-011-6368-7 · Cited by 15
Peroxisome proliferator-activated receptors and the vascular system: beyond their metabolic effects.
Marchesi, C., & Schiffrin, E. (2008) · Journal of the American Society of Hypertension : JASH · doi:10.1016/j.jash.2007.12.007 · Cited by 17
(2005) · PubMed Central · Cited by 15
Self-citationEffect of fenofibrate on serum nitric oxide levels in patients with hypertriglyceridemia
Esenboğa, K., Çiçek, Ö. F., Oktay, A. A., Ayral, P. A., & Gürlek, A. (2019) · Advances in Clinical and Experimental Medicine · doi:10.17219/acem/94161 · Cited by 14
Fenofibrate improves vascular endothelial function in diabetic mice
Xin, R., An, D., Li, Y., Fu, J., Huang, F., & Zhu, Q. (2019) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2019.108722 · Cited by 15
Herminghaus, A., Laser, E., Schulz, J., Truse, R., Vollmer, C., Bauer, I., & Picker, O. (2019) · Cells · doi:10.3390/cells8090983 · Cited by 14
Watts, G. F., & Staels, B. (2004) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.0000125706.86492.69 · Cited by 14
Effects of low and high doses of fenofibrate on protein, amino acid, and energy metabolism in rat
Holeček, M., & Vodeničarovová, M. (2020) · International Journal of Experimental Pathology · doi:10.1111/iep.12368 · Cited by 13
Zahedi, S. G., Koohdani, F., Qorbani, M., Nasli‐Esfahani, E., Aghasi, M., Khoshamal, H., Keshavarz, A. A., & Sotoudeh, G. (2022) · Journal of Herbal Medicine · doi:10.1016/j.hermed.2022.100555 · Cited by 14
González-Aparicio, R., Flores, J. A., Tasset, I., Túnez, I., & Fernández-Espejo, E. (2011) · Neuroscience · doi:10.1016/j.neuroscience.2011.03.062 · Cited by 13
del Campo, L., Blanco‐Rivero, J., & Balfagón, G. (2011) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2011.03.056 · Cited by 12
Hashizume, S., Akaike, M., Azuma, H., Ishikawa, K., Yoshida, S., Sumitomo-Ueda, Y., Yagi, S., Ikeda, Y., Iwase, T., Aihara, K., et al. (2011) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.5868 · Cited by 12
PPARα: its role in the human metabolic syndrome
Azhar, S., & Kelley, G. (2007) · Future Lipidology · doi:10.2217/17460875.2.1.31 · Cited by 12
Cervantes-Pérez, L. G., Ibarra-Lara, L., Escalante, B., del Valle‐Mondragón, L., Vargas‐Robles, H., Pérez‐Severiano, F., Pastelı́n, G., & Sánchez-Mendoza, A. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.04.006 · Cited by 12
Fenofibrate Reverses Dysfunction of EPCs Caused by Chronic Heart Failure
Huang, W., Yin, W., Chen, J.-S., Huang, P., Chen, J., & Lin, S. (2019) · Journal of Cardiovascular Translational Research · doi:10.1007/s12265-019-09889-y · Cited by 12
Reichenbach, G., Starzinski‐Powitz, A., Sloane, B. F., Doll, M., Kippenberger, S., Bernd, A., Kaufmann, R., & Meißner, M. (2012) · Angiogenesis · doi:10.1007/s10456-012-9314-9 · Cited by 12
How PPAR-alpha mediated inflammation may affect the pathophysiology of chronic kidney disease
Masenga, S. K., Desta, S., Hatcher, M. D., Kirabo, A., & Lee, D. L. (2024) · Current Research in Physiology · doi:10.1016/j.crphys.2024.100133 · Cited by 16
Becker, J., Delayre‐Orthez, C., Frossard, N., & Pons, F. (2011) · Fundamental and Clinical Pharmacology · doi:10.1111/j.1472-8206.2011.00935.x · Cited by 11
Jin, C., Zhao, R., Hu, W., Wu, X., Zhou, L., Shan, L., & Wu, H. (2024) · Drug Design Development and Therapy · doi:10.2147/dddt.s474628 · Cited by 9
Tauber, Z., Kolečková, M., & Čížková, K. (2019) · Medical Molecular Morphology · doi:10.1007/s00795-019-00240-7 · Cited by 9
Comparative cardiometabolic effects of fibrates and omega-3 fatty acids
Han, S. H., Oh, P. C., Lim, S. K., Eckel, R. H., & Koh, K. K. (2013) · International Journal of Cardiology · doi:10.1016/j.ijcard.2013.01.223 · Cited by 9
Fukuda, L. E., Davel, A. P., Veríssimo-Filho, S., Lopes, L. R., Cachofeiro, V., Lahera, V., & Rossoni, L. V. (2008) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e31818a8927 · Cited by 9
Adhikari, H., Patel, P., Javvaji, N., Crabtree, M. J., & Simon, J. N. (2025) · The Journal of Cardiovascular Aging · doi:10.20517/jca.2025.14 · Cited by 11
Yakubu, M. A., Nsaif, R. H., & Oyekan, A. (2010) · Bratislavské lekárske listy/Bratislava medical journal · doi:10.1007/bf03657365 · Cited by 8
Factors Modulating Fibrates Response: Therapeutic Implications and Alternative Strategies
Panadero, M. I., González, M. D. C., Herrera, E., & Bocos, C. (2009) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/187153009789044356 · Cited by 9
Restoration of Endothelial Function inPparα−/−Mice by Tempol
Silswal, N., Parelkar, N. K., Andresen, J. J., & Wacker, M. (2015) · PPAR Research · doi:10.1155/2015/728494 · Cited by 8
Qu, C., Leung, S. W. S., Vanhoutte, P. M., & Man, R. Y. K. (2012) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2012.09.015 · Cited by 9
Nitric Oxide in Vascular Damage and Regeneration
Claudio Napoli, A., Lerman, L. O., Balestrieri, M. L., & Ignarro, L. J. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-373866-0.00020-4 · Cited by 7
Cervantes-Pérez, L. G., Ibarra-Lara, L., Rubio, M. E., Escalante, B., Pérez‐Severiano, F., Soria‐Castro, E., Ramírez-Ortega, M. D. C., & Sánchez-Mendoza, M. A. (2010) · Pharmacological Reports · doi:10.1016/s1734-1140(10)70347-9 · Cited by 6
Anti-atherogenic properties of fibrates may be largely due to their anti-inflammatory effects
Ye, H., & Zhao, S. (2005) · Medical Hypotheses · doi:10.1016/j.mehy.2005.09.036 · Cited by 6
Bahia, L., Kraemer‐Aguiar, L. G., Villela, N. R., Bottino, D. A., Godoy‐Matos, A. F., & Bouskela, E. (2006) · Arquivos Brasileiros de Cardiologia · doi:10.1590/s0066-782x2006000500007 · Cited by 5
Zahradka, P. C. (2007) · Cardiovascular Drug Reviews · doi:10.1111/j.1527-3466.2007.00008.x · Cited by 5
Simonson, G., & Kendall, D. (2006) · Current Opinion in Endocrinology & Diabetes · doi:10.1097/01.med.0000216965.36504.be · Cited by 5
Modulación del PPARα por agentes farmacológicos y naturales y sus implicaciones metabólicas
Panadero, M. I., González, M. D. C., Herrera, E., & Bocos, C. (2008) · Clínica e Investigación en Arteriosclerosis · doi:10.1016/s0214-9168(08)75789-9 · Cited by 4
Interactions of PPAR α and GLUT4 in DOCA/salt-induced renal injury in mice.
Ighodaro, I., Eric, O., & Oyekan, A. (2013) · PubMed · Cited by 3
Microencapsulated Leukotrienes Augment Antimicrobial Activity against Infections
Nicolete, R., & Nicolete, L. D. D. F. (2012) · Journal of Cell Science & Therapy · doi:10.4172/2157-7013.s5-001 · Cited by 3
Sex-Specific Cardiovascular Protection in Developing Metabolic Syndrome: The Role of AMPK
Kvandová, M., Zemančíková, A., Berenyiová, A., Waczulı́ková, I., Magyarova, S., Mičurová, A., Török, J., Grman, M., Tomášová, L., Mišák, A., et al. (2025) · Antioxidants · doi:10.3390/antiox14070843 · Cited by 3
Tissue Distribution and Versatile Functions of PPARs
Youssef, J., & Badr, M. Z. (2013) · Humana Press eBooks · doi:10.1007/978-1-62703-420-3_5 · Cited by 2
Imig, J. D. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1186477 · Cited by 2
Role of PPARs in the Pathogenesis of the Metabolic Syndrome
Medina‐Gómez, G., Gray, S. L., & Vidal‐Puig, A. (2005) · Elsevier eBooks · doi:10.1016/b978-84-8174-892-5.50015-2 · Cited by 2
Cardiovascular Disease and Insulin Resistance
Ajjan, R., & Grant, P. J. (2007) · Springer eBooks · doi:10.1007/978-1-84628-715-2_138 · Cited by 2
Review: Vascular protective effects of peroxisome proliferator-activated receptor agonists
Cariou, B., Fruchart, J., & Staels, B. (2005) · The British Journal of Diabetes · doi:10.1177/14746514050050030301 · Cited by 2
Nakamura, A., Kagaya, Y., Saito, H., Kanazawa, M., Miura, M., Kondo, M., & Endo, H. (2026) · Frontiers in Endocrinology · doi:10.3389/fendo.2026.1750308 · Cited by 1
Self-citationAbo-Zaid, O. A., Hasanin, M., & Hanafi, A. (2013) · Journal of Investigational Biochemistry · doi:10.5455/jib.20130305012038 · Cited by 1
Yaribeygi, H., & Mohammadi, M. T. (2016) · Razavi International Journal of Medicine · doi:10.17795/rijm37670 · Cited by 1
Yang, Y., Cheng, Q., Liu, X., Liu, Z., Li, T., Jiang, X., & Wang, L. (2016) · Biomedical Chromatography · doi:10.1002/bmc.3777 · Cited by 1
Yilmaz, B. A., & Törüner, F. B. (2013) · CRC Press eBooks · doi:10.1201/b14907-9 · Cited by 1
Kuebart, A., Gross, K., Maicher, C., Sonnenschein, M., Raupach, A., Schulz, J., Truse, R., Hof, S., Marcus, C., Vollmer, C., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010262 · Cited by 1
Narce, M., & Poisson, J. (2004) · Current Opinion in Lipidology · doi:10.1097/00041433-200412000-00012 · Cited by 1
Illnait-Ferrer, J. (2014) · Revista CENIC. Ciencias biológicas
Gregoire, F. M. (2008) · PPAR Research · doi:10.1155/2008/736362
Fenofibrate Prevents Myocardial Ischemia-Reperfusion Injury in Rat Hearts
Gurfateh, S., Rohilla, A., & Razia, K. (2011)
Computational Drug Target Pathway Discovery: A Bayesian Network Approach
Imoto, S., Tamada, Y., Araki, H., & Miyano, S. (2011) · Springer eBooks · doi:10.1007/978-3-642-16345-6_24
Microencapsulated Leukotrienes Augment Antimicrobial Activity against
Montello, R. J. (2011)
Cardiovascular and mental health benefits of soy consumption: role of soy isoflavones.
Thorp, A. A. (2008) · Adelaide Research & Scholarship (AR&S) (University of Adelaide)
PHARMACOLOGICAL EFFECTS OF GEMFIBROZIL ON SOME CARDIOVASCULAR PREPARATIONS OF EXPERIMENTAL ANIMALS
Ouda, E. A. E.-A. (2016) · Al-Azhar Journal of Pharmaceutical Sciences/Al-Azhar Journal of Pharmaceutical Sciences · doi:10.21608/ajps.2016.6914
GOMAA, M. D. N. M. M. R. S., & Saeed, J. (2020) · The Medical Journal of Cairo University/The Medical Journal of Cairo University · doi:10.21608/mjcu.2020.110866
Cardiac transcriptomic remodeling in metabolic syndrome
Jaquet, K., Mügge, A., & Hamdani, N. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-822258-4.00011-0
Effects of Atorvastatin and Gemfibrozil on Mice Corpus Cavernosum In Vitro
Erkoseoglu, I., Kadıoğlu, M., Kesim, S. M., Yariş, E., & Kalyoncu, N. İ. (2025) · Fundamental and Clinical Pharmacology · doi:10.1111/fcp.70042
Metadata
- Authors
- Goya, K., Sumitani, S., Xu, X., Kitamura, T., Yamamoto, H., Kurebayashi, S., Saito, H., Kouhara, H., Kasayama, S., & Kawase, I.
- Affiliations
- The University of Osaka (JP)
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2004-04
- Volume
- 24
- Issue
- 4
- Pages
- 658-663
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2110733021
- Cited by
- 174
- References
- 47
- Citations by year
- 2026: 1 · 2025: 4 · 2024: 4 · 2023: 6 · 2022: 4 · 2021: 5 · 2020: 6 · 2019: 9 · 2017: 1 · 2016: 7 · 2015: 4 · 2014: 7 · 2013: 13 · 2012: 16
- FWCI
- 5.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Paraoxonase enzyme and polymorphisms
- Keywords
- PPARα agonist, endothelial nitric oxide synthase, fenofibrate, bezafibrate, Wy-14,643, rosiglitazone, RU486, vascular endothelial cells, cardioprotection
- MeSH terms
- Rosiglitazone, Animals, Aorta, Bezafibrate, Cattle, Cells, Cultured, Dactinomycin, Endothelium, Vascular, Enzyme Induction, Half-Life, Nitric Oxide, Fenofibrate, Pyrimidines, RNA, Messenger, Transcription Factors, Transcription, Genetic, Transfection, Mifepristone, Gene Expression Regulation, Enzymologic, Receptors, Cytoplasmic and Nuclear, Nitric Oxide Synthase, Endothelial Cells, Thiazolidinediones, Nitric Oxide Synthase Type III
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review