{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T02:15:11Z","timestamp":1789524911965,"version":"build-2803163510"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:00:00Z","timestamp":1600300800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T00:00:00Z","timestamp":1600300800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Graduate School of Health, Aarhus University"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Endothelial dysfunction is recognized as a major contributor to atherosclerosis and has been suggested to be evident far before plaque formation. Endothelial dysfunction in small resistance arteries has been suggested to initiate long before changes in conduit arteries. In this study, we address early changes in endothelial function of atherosclerosis prone rats. Male ApoE knockout (KO) rats (11- to 13-weeks-old) were subjected to either a Western or standard diet. The diet intervention continued for a period of 20\u201324\u00a0weeks. Endothelial function of pulmonary and mesenteric arteries was examined in vitro using an isometric myograph. We found that Western diet decreased the contribution of cyclooxygenase (COX) to control the vascular tone of both pulmonary and mesenteric arteries. These changes were associated with early stage atherosclerosis and elevated level of plasma total cholesterol, LDL and triglyceride in ApoE KO rats. Chondroid-transformed smooth muscle cells, calcifications, macrophages accumulation and foam cells were also observed in the aortic arch from ApoE KO rats fed Western diet. The ApoE KO rats are a new model to study endothelial dysfunction during the earlier stages of atherosclerosis and could help us improve preclinical drug development.<\/jats:p>","DOI":"10.1038\/s41598-020-72338-3","type":"journal-article","created":{"date-parts":[[2020,9,17]],"date-time":"2020-09-17T21:28:45Z","timestamp":1600378125000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":39,"title":["Endothelial dysfunction in small arteries and early signs\u00a0 of atherosclerosis in ApoE knockout rats"],"prefix":"10.1038","volume":"10","author":[{"given":"Simin","family":"Berenji Ardestani","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ingrid","family":"Eftedal","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Pedersen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Per Bendix","family":"Jeppesen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikke","family":"N\u00f8rregaard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir V.","family":"Matchkov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2020,9,17]]},"reference":[{"key":"72338_CR1","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jacc.2017.04.052","volume":"70","author":"GA Roth","year":"2017","unstructured":"Roth, G. A. et al. Global, Regional, and National Burden of Cardiovascular Diseases for 10 Causes, 1990 to 2015. J. Am. Coll. Cardiol. 70, 1\u201325. https:\/\/doi.org\/10.1016\/j.jacc.2017.04.052 (2017).","journal-title":"J. Am. Coll. Cardiol."},{"key":"72338_CR2","doi-asserted-by":"publisher","first-page":"1159","DOI":"10.1161\/01.RES.0000020401.61826.EA","volume":"90","author":"A Csiszar","year":"2002","unstructured":"Csiszar, A. et al. Aging-induced phenotypic changes and oxidative stress impair coronary arteriolar function. Circ. Res. 90, 1159\u20131166 (2002).","journal-title":"Circ. Res."},{"key":"72338_CR3","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1161\/01.CIR.0000131515.03336.f8","volume":"109","author":"J Davignon","year":"2004","unstructured":"Davignon, J. & Ganz, P. Role of endothelial dysfunction in atherosclerosis. Circulation 109, 27\u201332. https:\/\/doi.org\/10.1161\/01.CIR.0000131515.03336.f8 (2004).","journal-title":"Circulation"},{"key":"72338_CR4","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1038\/362801a0","volume":"362","author":"R Ross","year":"1993","unstructured":"Ross, R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature 362, 801\u2013809. https:\/\/doi.org\/10.1038\/362801a0 (1993).","journal-title":"Nature"},{"key":"72338_CR5","doi-asserted-by":"publisher","first-page":"55","DOI":"10.3389\/fphar.2018.00055","volume":"9","author":"C Fava","year":"2018","unstructured":"Fava, C. & Montagnana, M. Atherosclerosis is an inflammatory disease which lacks a common anti-inflammatory therapy: how human genetics can help to this issue. A narrative review. Front. Pharmacol. 9, 55. https:\/\/doi.org\/10.3389\/fphar.2018.00055 (2018).","journal-title":"Front. Pharmacol."},{"key":"72338_CR6","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.ijcha.2018.03.003","volume":"19","author":"M Vaccarezza","year":"2018","unstructured":"Vaccarezza, M., Balla, C. & Rizzo, P. Atherosclerosis as an inflammatory disease: doubts? No more. Int. J. Cardiol. Heart Vasc. 19, 1\u20132. https:\/\/doi.org\/10.1016\/j.ijcha.2018.03.003 (2018).","journal-title":"Int. J. Cardiol. Heart Vasc."},{"key":"72338_CR7","doi-asserted-by":"publisher","first-page":"2045","DOI":"10.1161\/atvbaha.108.179705","volume":"32","author":"P Libby","year":"2012","unstructured":"Libby, P. Inflammation in atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 32, 2045\u20132051. https:\/\/doi.org\/10.1161\/atvbaha.108.179705 (2012).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"72338_CR8","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1056\/nejm198602203140806","volume":"314","author":"R Ross","year":"1986","unstructured":"Ross, R. The pathogenesis of atherosclerosis\u2013an update. N. Engl. J. Med. 314, 488\u2013500. https:\/\/doi.org\/10.1056\/nejm198602203140806 (1986).","journal-title":"N. Engl. J. Med."},{"key":"72338_CR9","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1056\/nejm199901143400207","volume":"340","author":"R Ross","year":"1999","unstructured":"Ross, R. Atherosclerosis\u2013an inflammatory disease. N. Engl. J. Med. 340, 115\u2013126. https:\/\/doi.org\/10.1056\/nejm199901143400207 (1999).","journal-title":"N. Engl. J. Med."},{"key":"72338_CR10","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.arr.2009.07.002","volume":"9","author":"MD Herrera","year":"2010","unstructured":"Herrera, M. D., Mingorance, C., Rodriguez-Rodriguez, R. & Alvarez de Sotomayor, M. Endothelial dysfunction and aging: an update. Ageing Res Rev 9, 142\u2013152. https:\/\/doi.org\/10.1016\/j.arr.2009.07.002 (2010).","journal-title":"Ageing Res Rev"},{"key":"72338_CR11","doi-asserted-by":"publisher","first-page":"1752","DOI":"10.1172\/jci113516","volume":"81","author":"H Yamamoto","year":"1988","unstructured":"Yamamoto, H., Bossaller, C., Cartwright, J. Jr. & Henry, P. D. Videomicroscopic demonstration of defective cholinergic arteriolar vasodilation in atherosclerotic rabbit. J. Clin. Investig. 81, 1752\u20131758. https:\/\/doi.org\/10.1172\/jci113516 (1988).","journal-title":"J. Clin. Investig."},{"key":"72338_CR12","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1172\/JCI116156","volume":"91","author":"DG Harrison","year":"1993","unstructured":"Harrison, D. G. Endothelial dysfunction in the coronary microcirculation: a new clinical entity or an experimental finding?. J. Clin. Investig. 91, 1\u20132. https:\/\/doi.org\/10.1172\/JCI116156 (1993).","journal-title":"J. Clin. Investig."},{"key":"72338_CR13","doi-asserted-by":"publisher","first-page":"479","DOI":"10.3892\/br.2016.614","volume":"4","author":"AR Malik","year":"2016","unstructured":"Malik, A. R. Association of increased lipid peroxide levels in the aorta in comparison to the pulmonary artery with the presence of coronary artery disease. Biomed. Rep. 4, 479\u2013484. https:\/\/doi.org\/10.3892\/br.2016.614 (2016).","journal-title":"Biomed. Rep."},{"key":"72338_CR14","first-page":"139","volume":"142","author":"D Langleben","year":"1990","unstructured":"Langleben, D. Atherosclerosis and the lung. Cmaj 142, 139 (1990).","journal-title":"Cmaj"},{"key":"72338_CR15","doi-asserted-by":"publisher","first-page":"1104","DOI":"10.1161\/atvbaha.111.237693","volume":"32","author":"GS Getz","year":"2012","unstructured":"Getz, G. S. & Reardon, C. A. Animal models of atherosclerosis. Arterioscler. Thromb. Vasc. Biol. 32, 1104\u20131115. https:\/\/doi.org\/10.1161\/atvbaha.111.237693 (2012).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"72338_CR16","doi-asserted-by":"publisher","first-page":"1019","DOI":"10.1124\/jpet.105.098798","volume":"317","author":"B Lorkowska","year":"2006","unstructured":"Lorkowska, B. et al. Hypercholesterolemia does not alter endothelial function in spontaneously hypertensive rats. J. Pharmacol. Exp. Ther. 317, 1019\u20131026. https:\/\/doi.org\/10.1124\/jpet.105.098798 (2006).","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"72338_CR17","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.1161\/01.ATV.0000128849.12617.f4","volume":"24","author":"KS Meir","year":"2004","unstructured":"Meir, K. S. & Leitersdorf, E. Atherosclerosis in the apolipoprotein-E-deficient mouse: a decade of progress. Arterioscler. Thromb. Vasc. Biol. 24, 1006\u20131014. https:\/\/doi.org\/10.1161\/01.ATV.0000128849.12617.f4 (2004).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"72338_CR18","doi-asserted-by":"publisher","first-page":"4471","DOI":"10.1073\/pnas.89.10.4471","volume":"89","author":"JA Piedrahita","year":"1992","unstructured":"Piedrahita, J. A., Zhang, S. H., Hagaman, J. R., Oliver, P. M. & Maeda, N. Generation of mice carrying a mutant apolipoprotein E gene inactivated by gene targeting in embryonic stem cells. Proc. Natl. Acad. Sci. USA. 89, 4471\u20134475. https:\/\/doi.org\/10.1073\/pnas.89.10.4471 (1992).","journal-title":"Proc. Natl. Acad. Sci. USA."},{"key":"72338_CR19","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1038\/nbt.2786","volume":"32","author":"M Hay","year":"2014","unstructured":"Hay, M., Thomas, D. W., Craighead, J. L., Economides, C. & Rosenthal, J. Clinical development success rates for investigational drugs. Nat. Biotechnol. 32, 40\u201351. https:\/\/doi.org\/10.1038\/nbt.2786 (2014).","journal-title":"Nat. Biotechnol."},{"key":"72338_CR20","doi-asserted-by":"publisher","first-page":"2628","DOI":"10.1038\/s41598-019-38732-2","volume":"9","author":"JG Lee","year":"2019","unstructured":"Lee, J. G. et al. Knockout rat models mimicking human atherosclerosis created by Cpf1-mediated gene targeting. Sci. Rep. 9, 2628. https:\/\/doi.org\/10.1038\/s41598-019-38732-2 (2019).","journal-title":"Sci. Rep."},{"key":"72338_CR21","doi-asserted-by":"publisher","first-page":"589","DOI":"10.1016\/j.atherosclerosis.2015.10.093","volume":"243","author":"S Wei","year":"2015","unstructured":"Wei, S. et al. Apolipoprotein E-deficient rats develop atherosclerotic plaques in partially ligated carotid arteries. Atherosclerosis 243, 589\u2013592. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2015.10.093 (2015).","journal-title":"Atherosclerosis"},{"key":"72338_CR22","doi-asserted-by":"publisher","first-page":"5416","DOI":"10.1038\/s41598-018-23835-z","volume":"8","author":"I Rune","year":"2018","unstructured":"Rune, I. et al. Long-term Western diet fed apolipoprotein E-deficient rats exhibit only modest early atherosclerotic characteristics. Sci. Rep. 8, 5416. https:\/\/doi.org\/10.1038\/s41598-018-23835-z (2018).","journal-title":"Sci. Rep."},{"key":"72338_CR23","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.atherosclerosis.2018.02.015","volume":"271","author":"Y Zhao","year":"2018","unstructured":"Zhao, Y. et al. Hyperlipidemia induces typical atherosclerosis development in Ldlr and Apoe deficient rats. Atherosclerosis 271, 26\u201335. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2018.02.015 (2018).","journal-title":"Atherosclerosis"},{"key":"72338_CR24","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1111\/j.1476-5381.1988.tb11535.x","volume":"94","author":"L Jayakody","year":"1988","unstructured":"Jayakody, L., Kappagoda, T., Senaratne, M. P. & Thomson, A. B. Impairment of endothelium-dependent relaxation: an early marker for atherosclerosis in the rabbit. Br. J. Pharmacol. 94, 335\u2013346. https:\/\/doi.org\/10.1111\/j.1476-5381.1988.tb11535.x (1988).","journal-title":"Br. J. Pharmacol."},{"key":"72338_CR25","doi-asserted-by":"publisher","first-page":"1070","DOI":"10.1016\/j.bbalip.2006.06.013","volume":"1761","author":"J Lie","year":"2006","unstructured":"Lie, J. et al. Sex differences in atherosclerosis in mice with elevated phospholipid transfer protein activity are related to decreased plasma high density lipoproteins and not to increased production of triglycerides. Biochim. Biophys. Acta. 1761, 1070\u20131077. https:\/\/doi.org\/10.1016\/j.bbalip.2006.06.013 (2006).","journal-title":"Biochim. Biophys. Acta."},{"key":"72338_CR26","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1186\/1476-511x-9-87","volume":"9","author":"TM Pereira","year":"2010","unstructured":"Pereira, T. M. et al. Cardiac and vascular changes in elderly atherosclerotic mice: the influence of gender. Lipids Health Dis. 9, 87. https:\/\/doi.org\/10.1186\/1476-511x-9-87 (2010).","journal-title":"Lipids Health Dis."},{"key":"72338_CR27","doi-asserted-by":"publisher","first-page":"985","DOI":"10.1152\/ajpheart.00292.2006","volume":"291","author":"M Feletou","year":"2006","unstructured":"Feletou, M. & Vanhoutte, P. M. Endothelial dysfunction: a multifaceted disorder (The Wiggers Award Lecture). Am. J. Physiol. Heart Circul Physiol 291, 985\u20131002. https:\/\/doi.org\/10.1152\/ajpheart.00292.2006 (2006).","journal-title":"Am. J. Physiol. Heart Circul Physiol"},{"key":"72338_CR28","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1007\/s000180050358","volume":"55","author":"JF Arnal","year":"1999","unstructured":"Arnal, J. F., Dinh-Xuan, A. T., Pueyo, M., Darblade, B. & Rami, J. Endothelium-derived nitric oxide and vascular physiology and pathology. Cell Mol. Life Sci. 55, 1078\u20131087 (1999).","journal-title":"Cell Mol. Life Sci."},{"key":"72338_CR29","doi-asserted-by":"publisher","first-page":"373","DOI":"10.1038\/288373a0","volume":"288","author":"RF Furchgott","year":"1980","unstructured":"Furchgott, R. F. & Zawadzki, J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature 288, 373\u2013376. https:\/\/doi.org\/10.1038\/288373a0 (1980).","journal-title":"Nature"},{"key":"72338_CR30","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1161\/01.ATV.17.11.2333","volume":"17","author":"S Bonthu","year":"1997","unstructured":"Bonthu, S., Heistad, D. D., Chappell, D. A., Lamping, K. G. & Faraci, F. M. Atherosclerosis, vascular remodeling, and impairment of endothelium-dependent relaxation in genetically altered hyperlipidemic mice. Arterioscler. Thromb. Vasc. Biol. 17, 2333\u20132340 (1997).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"72338_CR31","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/s0021-9150(02)00178-8","volume":"164","author":"ME Rosenfeld","year":"2002","unstructured":"Rosenfeld, M. E. et al. Estrogen inhibits the initiation of fatty streaks throughout the vasculature but does not inhibit intra-plaque hemorrhage and the progression of established lesions in apolipoprotein E deficient mice. Atherosclerosis 164, 251\u2013259. https:\/\/doi.org\/10.1016\/s0021-9150(02)00178-8 (2002).","journal-title":"Atherosclerosis"},{"key":"72338_CR32","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1161\/01.ATV.21.6.1017","volume":"21","author":"LV d'Uscio","year":"2001","unstructured":"d\u2019Uscio, L. V. et al. Mechanism of endothelial dysfunction in apolipoprotein E-deficient mice. Arterioscler. Thromb. Vasc. Biol. 21, 1017\u20131022 (2001).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"72338_CR33","doi-asserted-by":"publisher","first-page":"2658","DOI":"10.1161\/hs1101.097393","volume":"32","author":"LV d'Uscio","year":"2001","unstructured":"d\u2019Uscio, L. V., Smith, L. A. & Katusic, Z. S. Hypercholesterolemia impairs endothelium-dependent relaxations in common carotid arteries of apolipoprotein e-deficient mice. Stroke 32, 2658\u20132664. https:\/\/doi.org\/10.1161\/hs1101.097393 (2001).","journal-title":"Stroke"},{"key":"72338_CR34","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2019.01342","author":"S Berenji Ardestani","year":"2019","unstructured":"Berenji Ardestani, S., Matchkov, V. V., Eftedal, I. & Pedersen, M. a single simulated heliox dive modifies endothelial function in the vascular wall of apoe knockout male rats more than females. Front. Physiol https:\/\/doi.org\/10.3389\/fphys.2019.01342 (2019).","journal-title":"Front. Physiol"},{"key":"72338_CR35","doi-asserted-by":"publisher","first-page":"834","DOI":"10.1038\/sj.bjp.0706390","volume":"146","author":"P Gluais","year":"2005","unstructured":"Gluais, P., Lonchampt, M., Morrow, J. D., Vanhoutte, P. M. & Feletou, M. Acetylcholine-induced endothelium-dependent contractions in the SHR aorta: the Janus face of prostacyclin. Br. J. Pharmacol. 146, 834\u2013845. https:\/\/doi.org\/10.1038\/sj.bjp.0706390 (2005).","journal-title":"Br. J. Pharmacol."},{"key":"72338_CR36","doi-asserted-by":"publisher","first-page":"894","DOI":"10.1111\/j.1476-5381.2011.01276.x","volume":"164","author":"M F\u00e9l\u00e9tou","year":"2011","unstructured":"F\u00e9l\u00e9tou, M., Huang, Y. & Vanhoutte, P. M. Endothelium-mediated control of vascular tone: COX-1 and COX-2 products. Br. J. Pharmacol. 164, 894\u2013912. https:\/\/doi.org\/10.1111\/j.1476-5381.2011.01276.x (2011).","journal-title":"Br. J. Pharmacol."},{"key":"72338_CR37","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/sj.bjp.0704669","volume":"136","author":"D Yang","year":"2002","unstructured":"Yang, D. et al. Oxygen-derived free radicals mediate endothelium-dependent contractions to acetylcholine in aortas from spontaneously hypertensive rats. Br. J. Pharmacol. 136, 104\u2013110. https:\/\/doi.org\/10.1038\/sj.bjp.0704669 (2002).","journal-title":"Br. J. Pharmacol."},{"key":"72338_CR38","doi-asserted-by":"publisher","first-page":"449","DOI":"10.1038\/sj.bjp.0706042","volume":"144","author":"PM Vanhoutte","year":"2005","unstructured":"Vanhoutte, P. M., Feletou, M. & Taddei, S. Endothelium-dependent contractions in hypertension. Br. J. Pharmacol. 144, 449\u2013458. https:\/\/doi.org\/10.1038\/sj.bjp.0706042 (2005).","journal-title":"Br. J. Pharmacol."},{"key":"72338_CR39","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.atherosclerosis.2008.04.016","volume":"202","author":"S McClelland","year":"2009","unstructured":"McClelland, S. et al. Contribution of cyclooxygenase-1 to thromboxane formation, platelet-vessel wall interactions and atherosclerosis in the ApoE null mouse. Atherosclerosis 202, 84\u201391. https:\/\/doi.org\/10.1016\/j.atherosclerosis.2008.04.016 (2009).","journal-title":"Atherosclerosis"},{"key":"72338_CR40","doi-asserted-by":"publisher","first-page":"577","DOI":"10.2174\/1381612043453144","volume":"10","author":"FA Fitzpatrick","year":"2004","unstructured":"Fitzpatrick, F. A. Cyclooxygenase enzymes: regulation and function. Curr. Pharm Des. 10, 577\u2013588. https:\/\/doi.org\/10.2174\/1381612043453144 (2004).","journal-title":"Curr. Pharm Des."},{"key":"72338_CR41","doi-asserted-by":"publisher","first-page":"5295","DOI":"10.1113\/jphysiol.2008.161430","volume":"586","author":"PM Vanhoutte","year":"2008","unstructured":"Vanhoutte, P. M. & Tang, E. H. Endothelium-dependent contractions: when a good guy turns bad!. J. Physiol. 586, 5295\u20135304. https:\/\/doi.org\/10.1113\/jphysiol.2008.161430 (2008).","journal-title":"J. Physiol."},{"key":"72338_CR42","doi-asserted-by":"publisher","unstructured":"42van der Loo, B. et al. Enhanced peroxynitrite formation is associated with vascular aging. J Exp Med 192, 1731\u20131744, https:\/\/doi.org\/10.1084\/jem.192.12.1731 (2000).","DOI":"10.1084\/jem.192.12.1731"},{"key":"72338_CR43","doi-asserted-by":"publisher","first-page":"154","DOI":"10.1111\/j.1476-5381.2009.00525.x","volume":"159","author":"E Brondum","year":"2010","unstructured":"Brondum, E., Kold-Petersen, H., Simonsen, U. & Aalkjaer, C. NS309 restores EDHF-type relaxation in mesenteric small arteries from type 2 diabetic ZDF rats. Br. J. Pharmacol. 159, 154\u2013165. https:\/\/doi.org\/10.1111\/j.1476-5381.2009.00525.x (2010).","journal-title":"Br. J. Pharmacol."},{"key":"72338_CR44","doi-asserted-by":"publisher","first-page":"1082","DOI":"10.1111\/j.1440-1681.1996.tb01174.x","volume":"23","author":"M Feletou","year":"1996","unstructured":"Feletou, M. & Vanhoutte, P. M. Endothelium-derived hyperpolarizing factor. Clin. Exp. Pharmacol. Physiol. 23, 1082\u20131090. https:\/\/doi.org\/10.1111\/j.1440-1681.1996.tb01174.x (1996).","journal-title":"Clin. Exp. Pharmacol. Physiol."},{"key":"72338_CR45","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1038\/oby.2005.121","volume":"13","author":"EM Van Schothorst","year":"2005","unstructured":"Van Schothorst, E. M. et al. Adipose gene expression patterns of weight gain suggest counteracting steroid hormone synthesis. Obes. Res. 13, 1031\u20131041. https:\/\/doi.org\/10.1038\/oby.2005.121 (2005).","journal-title":"Obes. Res."},{"key":"72338_CR46","doi-asserted-by":"publisher","first-page":"1982","DOI":"10.1161\/atvbaha.108.169722","volume":"28","author":"F Kim","year":"2008","unstructured":"Kim, F. et al. Vascular inflammation, insulin resistance, and reduced nitric oxide production precede the onset of peripheral insulin resistance. Arterioscler. Thromb. Vasc. Biol. 28, 1982\u20131988. https:\/\/doi.org\/10.1161\/atvbaha.108.169722 (2008).","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"issue":"Suppl 4","key":"72338_CR47","doi-asserted-by":"publisher","first-page":"S14","DOI":"10.1186\/ar1794","volume":"7","author":"JS Borer","year":"2005","unstructured":"Borer, J. S. & Simon, L. S. Cardiovascular and gastrointestinal effects of COX-2 inhibitors and NSAIDs: achieving a balance. Arthritis. Res. Ther. 7(Suppl 4), S14-22. https:\/\/doi.org\/10.1186\/ar1794 (2005).","journal-title":"Arthritis. Res. Ther."},{"key":"72338_CR48","doi-asserted-by":"publisher","first-page":"85","DOI":"10.1007\/978-1-4939-2929-0_5","volume":"1339","author":"MJ Andres-Manzano","year":"2015","unstructured":"Andres-Manzano, M. J., Andres, V. & Dorado, B. Oil red O and hematoxylin and eosin staining for quantification of atherosclerosis burden in mouse aorta and aortic root. Methods Mol. Biol. 1339, 85\u201399. https:\/\/doi.org\/10.1007\/978-1-4939-2929-0_5 (2015).","journal-title":"Methods Mol. Biol."},{"key":"72338_CR49","doi-asserted-by":"publisher","first-page":"F259","DOI":"10.1152\/ajprenal.00352.2013","volume":"306","author":"M Ostergaard","year":"2014","unstructured":"Ostergaard, M. et al. ROS dependence of cyclooxygenase-2 induction in rats subjected to unilateral ureteral obstruction. Am. J. Physiol. Renal Physiol. 306, F259-270. https:\/\/doi.org\/10.1152\/ajprenal.00352.2013 (2014).","journal-title":"Am. J. Physiol. Renal Physiol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72338-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72338-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72338-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,6]],"date-time":"2022-12-06T18:47:29Z","timestamp":1670352449000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-020-72338-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,17]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2020,12]]}},"alternative-id":["72338"],"URL":"https:\/\/doi.org\/10.1038\/s41598-020-72338-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,17]]},"assertion":[{"value":"19 February 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 August 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"15296"}}