{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T04:21:42Z","timestamp":1772166102285,"version":"3.50.1"},"reference-count":45,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:00:00Z","timestamp":1601078400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T00:00:00Z","timestamp":1601078400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Kowa Company. Ltd."}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cardiovasc Diabetol"],"published-print":{"date-parts":[[2020,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Statins suppress the progression of atherosclerosis by reducing low-density lipoprotein (LDL) cholesterol levels. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor \u03b1 modulator, is expected to reduce residual risk factors including high triglycerides (TGs) and low high-density lipoprotein (HDL) cholesterol during statin treatment. However, it is not known if statin therapy with add-on pemafibrate improves the progression of atherosclerosis. The aim of this study was to assess the effect of combination therapy with pitavastatin and pemafibrate on lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Seven-week-old male Dahl salt-sensitive (DS) rats were divided into the following five treatment groups (normal diet (ND) plus vehicle, high-salt and high-fat diet (HD) plus vehicle, HD plus pitavastatin (0.3\u00a0mg\/kg\/day), HD plus pemafibrate (K-877) (0.5\u00a0mg\/kg\/day), and HD plus combination of pitavastatin and pemafibrate) and treated for 12\u00a0weeks. At 19\u00a0weeks, endothelium-dependent relaxation of the thoracic aorta in response to acetylcholine was evaluated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>After feeding for 12\u00a0weeks, systolic blood pressure and plasma levels of total cholesterol were significantly higher in the HD-vehicle group compared with the ND-vehicle group. Combination therapy with pitavastatin and pemafibrate significantly reduced systolic blood pressure, TG levels, including total, chylomicron (CM), very LDL (VLDL), HDL-TG, and cholesterol levels, including total, CM, VLDL, and LDL-cholesterol, compared with vehicle treatment. Acetylcholine caused concentration-dependent relaxation of thoracic aorta rings that were pre-contracted with phenylephrine in all rats. Relaxation rates in the HD-vehicle group were significantly lower compared with the ND-vehicle group. Relaxation rates in the HD-combination of pitavastatin and pemafibrate group significantly increased compared with the HD-vehicle group, although neither medication alone ameliorated relaxation rates significantly. Western blotting experiments showed increased phosphorylated endothelial nitric oxide synthase protein expression in aortas from rats in the HD-pemafibrate group and the HD-combination group compared with the HD-vehicle group. However, the expression levels did not respond significantly to pitavastatin alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Combination therapy with pitavastatin and pemafibrate improved lipid profiles and endothelial dysfunction in hypertension and insulin resistance model rats. Pemafibrate as an add-on strategy to statins may be useful for preventing atherosclerosis progression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-020-01132-2","type":"journal-article","created":{"date-parts":[[2020,9,26]],"date-time":"2020-09-26T10:03:38Z","timestamp":1601114618000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Combination therapy with pemafibrate (K-877) and pitavastatin improves vascular endothelial dysfunction in dahl\/salt-sensitive rats fed a high-salt and high-fat diet"],"prefix":"10.1186","volume":"19","author":[{"given":"Masatoki","family":"Yoshida","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8845-3626","authenticated-orcid":false,"given":"Kazufumi","family":"Nakamura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toru","family":"Miyoshi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masashi","family":"Yoshida","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megumi","family":"Kondo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru","family":"Akazawa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tomonari","family":"Kimura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroaki","family":"Ohtsuka","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuko","family":"Ohno","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiji","family":"Miura","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroshi","family":"Ito","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,9,26]]},"reference":[{"issue":"9753","key":"1132_CR1","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1016\/S0140-6736(10)61350-5","volume":"376","author":"C Baigent","year":"2010","unstructured":"Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, Peto R, Barnes EH, Keech A, Simes J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet. 2010;376(9753):1670\u201381.","journal-title":"Lancet"},{"issue":"1","key":"1132_CR2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s11883-011-0219-7","volume":"14","author":"UK Sampson","year":"2012","unstructured":"Sampson UK, Fazio S, Linton MF. Residual cardiovascular risk despite optimal LDL cholesterol reduction with statins: the evidence, etiology, and therapeutic challenges. Curr Atheroscler Rep. 2012;14(1):1\u201310.","journal-title":"Curr Atheroscler Rep"},{"issue":"5","key":"1132_CR3","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1093\/aje\/153.5.490","volume":"153","author":"H Iso","year":"2001","unstructured":"Iso H, Naito Y, Sato S, Kitamura A, Okamura T, Sankai T, Shimamoto T, Iida M, Komachi Y. Serum triglycerides and risk of coronary heart disease among Japanese men and women. Am J Epidemiol. 2001;153(5):490\u20139.","journal-title":"Am J Epidemiol"},{"issue":"9943","key":"1132_CR4","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/S0140-6736(14)61177-6","volume":"384","author":"BG Nordestgaard","year":"2014","unstructured":"Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384(9943):626\u201335.","journal-title":"Lancet"},{"issue":"4","key":"1132_CR5","doi-asserted-by":"crossref","first-page":"335","DOI":"10.1016\/j.jjcc.2015.12.001","volume":"67","author":"K Nakamura","year":"2016","unstructured":"Nakamura K, Miyoshi T, Yunoki K, Ito H. Postprandial hyperlipidemia as a potential residual risk factor. J Cardiol. 2016;67(4):335\u20139.","journal-title":"J Cardiol"},{"issue":"2","key":"1132_CR6","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1016\/S0021-9150(00)00601-8","volume":"155","author":"JH Bae","year":"2001","unstructured":"Bae JH, Bassenge E, Kim KB, Kim YN, Kim KS, Lee HJ, Moon KC, Lee MS, Park KY, Schwemmer M. Postprandial hypertriglyceridemia impairs endothelial function by enhanced oxidant stress. Atherosclerosis. 2001;155(2):517\u201323.","journal-title":"Atherosclerosis"},{"issue":"3","key":"1132_CR7","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1194\/jlr.M200419-JLR200","volume":"44","author":"AJ van Oostrom","year":"2003","unstructured":"van Oostrom AJ, Sijmonsma TP, Verseyden C, Jansen EH, de Koning EJ, Rabelink TJ, Castro Cabezas M. Postprandial recruitment of neutrophils may contribute to endothelial dysfunction. J Lipid Res. 2003;44(3):576\u201383.","journal-title":"J Lipid Res"},{"issue":"19","key":"1132_CR8","doi-asserted-by":"crossref","first-page":"2518","DOI":"10.1161\/01.CIR.0000165070.46111.9F","volume":"111","author":"A Ceriello","year":"2005","unstructured":"Ceriello A, Assaloni R, Da Ros R, Maier A, Piconi L, Quagliaro L, Esposito K, Giugliano D. Effect of atorvastatin and irbesartan, alone and in combination, on postprandial endothelial dysfunction, oxidative stress, and inflammation in type 2 diabetic patients. Circulation. 2005;111(19):2518\u201324.","journal-title":"Circulation"},{"issue":"2","key":"1132_CR9","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.atherosclerosis.2006.09.015","volume":"193","author":"GD Norata","year":"2007","unstructured":"Norata GD, Grigore L, Raselli S, Redaelli L, Hamsten A, Maggi F, Eriksson P, Catapano AL. Post-prandial endothelial dysfunction in hypertriglyceridemic subjects: molecular mechanisms and gene expression studies. Atherosclerosis. 2007;193(2):321\u20137.","journal-title":"Atherosclerosis"},{"issue":"1\u20132","key":"1132_CR10","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/j.cccn.2003.08.014","volume":"338","author":"N Ohara","year":"2003","unstructured":"Ohara N, Takeichi S, Naito Y, Nakajima Y, Yukawa N, Nakano T, Nakajima K. Remnant-like particles from subjects who died of coronary artery disease suppress NO synthase activity and attenuate endothelium-dependent vasorelaxation. Clin Chim Acta. 2003;338(1\u20132):151\u20136.","journal-title":"Clin Chim Acta"},{"issue":"8","key":"1132_CR11","doi-asserted-by":"crossref","first-page":"1673","DOI":"10.1194\/jlr.R700001-JLR200","volume":"48","author":"XY Zheng","year":"2007","unstructured":"Zheng XY, Liu L. Remnant-like lipoprotein particles impair endothelial function: direct and indirect effects on nitric oxide synthase. J Lipid Res. 2007;48(8):1673\u201380.","journal-title":"J Lipid Res"},{"issue":"2","key":"1132_CR12","doi-asserted-by":"crossref","first-page":"486","DOI":"10.1016\/j.atherosclerosis.2011.04.019","volume":"217","author":"K Yunoki","year":"2011","unstructured":"Yunoki K, Nakamura K, Miyoshi T, Enko K, Kohno K, Morita H, Kusano KF, Ito H. Ezetimibe improves postprandial hyperlipemia and its induced endothelial dysfunction. Atherosclerosis. 2011;217(2):486\u201391.","journal-title":"Atherosclerosis"},{"issue":"1","key":"1132_CR13","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/1475-2840-13-71","volume":"13","author":"Y Ohno","year":"2014","unstructured":"Ohno Y, Miyoshi T, Noda Y, Oe H, Toh N, Nakamura K, Kohno K, Morita H, Ito H. Bezafibrate improves postprandial hypertriglyceridemia and associated endothelial dysfunction in patients with metabolic syndrome: a randomized crossover study. Cardiovasc Diabetol. 2014;13(1):71.","journal-title":"Cardiovasc Diabetol"},{"issue":"5","key":"1132_CR14","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1161\/HYPERTENSIONAHA.118.11554","volume":"72","author":"A Tanaka","year":"2018","unstructured":"Tanaka A, Tomiyama H, Maruhashi T, Matsuzawa Y, Miyoshi T, Kabutoya T, Kario K, Sugiyama S, Munakata M, Ito H, et al. Physiological diagnostic criteria for vascular failure. Hypertension. 2018;72(5):1060\u201371.","journal-title":"Hypertension"},{"issue":"3","key":"1132_CR15","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1080\/14656566.2018.1428560","volume":"19","author":"N Katsiki","year":"2018","unstructured":"Katsiki N, Reiner Z, Tedeschi Reiner E, Al-Rasadi K, Pirro M, Mikhailidis DP, Sahebkar A. Improvement of endothelial function by pitavastatin: a meta-analysis. Expert Opin Pharmacother. 2018;19(3):279\u201386.","journal-title":"Expert Opin Pharmacother"},{"issue":"3","key":"1132_CR16","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1016\/j.jjcc.2019.08.006","volume":"75","author":"T Nakamura","year":"2020","unstructured":"Nakamura T, Uematsu M, Yoshizaki T, Kobayashi T, Watanabe Y, Kugiyama K. Improvement of endothelial dysfunction is mediated through reduction of remnant lipoprotein after statin therapy in patients with coronary artery disease. J Cardiol. 2020;75(3):270\u20134.","journal-title":"J Cardiol."},{"issue":"3","key":"1132_CR17","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1016\/j.amjcard.2011.03.049","volume":"108","author":"K Yunoki","year":"2011","unstructured":"Yunoki K, Nakamura K, Miyoshi T, Enko K, Kubo M, Murakami M, Hata Y, Kohno K, Morita H, Kusano KF, et al. Impact of hypertriglyceridemia on endothelial dysfunction during statin\u2009\u00b1\u2009ezetimibe therapy in patients with coronary heart disease. Am J Cardiol. 2011;108(3):333\u20139.","journal-title":"Am J Cardiol"},{"key":"1132_CR18","doi-asserted-by":"crossref","unstructured":"AccordStudyGroup, Ginsberg HN, Elam MB, Lovato LC, Crouse JR, 3rd, Leiter LA, Linz P, Friedewald WT, Buse JB, Gerstein HC et al: Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med 2010, 362(17):1563-1574.","DOI":"10.1056\/NEJMoa1001282"},{"issue":"1","key":"1132_CR19","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s12933-020-01002-x","volume":"19","author":"L Zhu","year":"2020","unstructured":"Zhu L, Hayen A, Bell KJL. Legacy effect of fibrate add-on therapy in diabetic patients with dyslipidemia: a secondary analysis of the ACCORDION study. Cardiovasc Diabetol. 2020;19(1):28.","journal-title":"Cardiovasc Diabetol"},{"issue":"1","key":"1132_CR20","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1186\/s12933-019-0864-7","volume":"18","author":"JC Fruchart","year":"2019","unstructured":"Fruchart JC, Santos RD, Aguilar-Salinas C, Aikawa M, Al Rasadi K, Amarenco P, Barter PJ, Ceska R, Corsini A, Despres JP, et al. The selective peroxisome proliferator-activated receptor alpha modulator (SPPARMalpha) paradigm: conceptual framework and therapeutic potential: a consensus statement from the International Atherosclerosis Society (IAS) and the Residual Risk Reduction Initiative (R3i) Foundation. Cardiovasc Diabetol. 2019;18(1):71.","journal-title":"Cardiovasc Diabetol"},{"issue":"1","key":"1132_CR21","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1186\/s12933-017-0602-y","volume":"16","author":"JC Fruchart","year":"2017","unstructured":"Fruchart JC. Pemafibrate (K-877), a novel selective peroxisome proliferator-activated receptor alpha modulator for management of atherogenic dyslipidaemia. Cardiovasc Diabetol. 2017;16(1):124.","journal-title":"Cardiovasc Diabetol"},{"issue":"1","key":"1132_CR22","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/j.jacl.2017.10.006","volume":"12","author":"Ishibashi S, Arai H, Yokote K, Araki E, Suganami H, Yamashita S, Group KS","year":"2018","unstructured":"Ishibashi S, Arai H, Yokote K, Araki E, Suganami H, Yamashita S, Group KS. Efficacy and safety of pemafibrate (K-877), a selective peroxisome proliferator-activated receptor alpha modulator, in patients with dyslipidemia: results from a 24-week, randomized, double blind, active-controlled, phase 3 trial. J Clin Lipidol. 2018;12(1):173\u201384.","journal-title":"J Clin Lipidol"},{"key":"1132_CR23","doi-asserted-by":"crossref","unstructured":"Yamashita S, Arai H, Yokote K, Araki E, Suganami H, Ishibashi S, Group KS: Effects of pemafibrate (K-877) on cholesterol efflux capacity and postprandial hyperlipidemia in patients with atherogenic dyslipidemia. J Clin Lipidol 2018, 12(5):1267-1279 e1264.","DOI":"10.1016\/j.jacl.2018.06.010"},{"issue":"5","key":"1132_CR24","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1080\/10641960902825487","volume":"31","author":"A Nagae","year":"2009","unstructured":"Nagae A, Fujita M, Kawarazaki H, Matsui H, Ando K, Fujita T. Effect of high fat loading in Dahl salt-sensitive rats. Clin Exp Hypertens. 2009;31(5):451\u201361.","journal-title":"Clin Exp Hypertens"},{"issue":"5","key":"1132_CR25","doi-asserted-by":"crossref","first-page":"e43","DOI":"10.1161\/HYPERTENSIONAHA.118.11485","volume":"72","author":"R Fernandes","year":"2018","unstructured":"Fernandes R, Garver H, Harkema JR, Galligan JJ, Fink GD, Xu H. Sex differences in renal inflammation and injury in high-fat diet-fed dahl salt-sensitive rats. Hypertension. 2018;72(5):e43\u201352.","journal-title":"Hypertension"},{"issue":"3","key":"1132_CR26","doi-asserted-by":"crossref","first-page":"728","DOI":"10.1536\/ihj.18-392","volume":"60","author":"T Kimura","year":"2019","unstructured":"Kimura T, Nakamura K, Miyoshi T, Yoshida M, Akazawa K, Saito Y, Akagi S, Ohno Y, Kondo M, Miura D, et al. Inhibitory effects of tofogliflozin on cardiac hypertrophy in dahl salt-sensitive and salt-resistant rats fed a high-fat diet. Int Heart J. 2019;60(3):728\u201335.","journal-title":"Int Heart J"},{"issue":"5","key":"1132_CR27","doi-asserted-by":"crossref","first-page":"805","DOI":"10.1016\/S0022-2275(20)30123-1","volume":"43","author":"S Usui","year":"2002","unstructured":"Usui S, Hara Y, Hosaki S, Okazaki M. A new on-line dual enzymatic method for simultaneous quantification of cholesterol and triglycerides in lipoproteins by HPLC. J Lipid Res. 2002;43(5):805\u201314.","journal-title":"J Lipid Res"},{"issue":"8","key":"1132_CR28","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1016\/j.biopha.2014.10.008","volume":"68","author":"T Miyoshi","year":"2014","unstructured":"Miyoshi T, Noda Y, Ohno Y, Sugiyama H, Oe H, Nakamura K, Kohno K, Ito H. Omega-3 fatty acids improve postprandial lipemia and associated endothelial dysfunction in healthy individuals\u2014a randomized cross-over trial. Biomed Pharmacother. 2014;68(8):1071\u20137.","journal-title":"Biomed Pharmacother"},{"issue":"8","key":"1132_CR29","doi-asserted-by":"crossref","first-page":"e0181009","DOI":"10.1371\/journal.pone.0181009","volume":"12","author":"K Nakamura","year":"2017","unstructured":"Nakamura K, Miura D, Saito Y, Yunoki K, Koyama Y, Satoh M, Kondo M, Osawa K, Hatipoglu OF, Miyoshi T, et al. Eicosapentaenoic acid prevents arterial calcification in klotho mutant mice. PLoS ONE. 2017;12(8):e0181009.","journal-title":"PLoS ONE"},{"key":"1132_CR30","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1016\/j.atherosclerosis.2016.02.029","volume":"249","author":"Ishibashi S, Yamashita S, Arai H, Araki E, Yokote K, Suganami H, Fruchart JC, Kodama T, Group KS","year":"2016","unstructured":"Ishibashi S, Yamashita S, Arai H, Araki E, Yokote K, Suganami H, Fruchart JC, Kodama T, Group KS. Effects of K-877, a novel selective PPARalpha modulator (SPPARMalpha), in dyslipidaemic patients: a randomized, double blind, active- and placebo-controlled, phase 2 trial. Atherosclerosis. 2016;249:36\u201343.","journal-title":"Atherosclerosis"},{"issue":"1","key":"1132_CR31","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s12933-019-0845-x","volume":"18","author":"S Ida","year":"2019","unstructured":"Ida S, Kaneko R, Murata K. Efficacy and safety of pemafibrate administration in patients with dyslipidemia: a systematic review and meta-analysis. Cardiovasc Diabetol. 2019;18(1):38.","journal-title":"Cardiovasc Diabetol"},{"issue":"4","key":"1132_CR32","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.jphs.2017.02.003","volume":"133","author":"K Takei","year":"2017","unstructured":"Takei K, Nakagawa Y, Wang Y, Han SI, Satoh A, Sekiya M, Matsuzaka T, Shimano H. Effects of K-877, a novel selective PPARalpha modulator, on small intestine contribute to the amelioration of hyperlipidemia in low-density lipoprotein receptor knockout mice. J Pharmacol Sci. 2017;133(4):214\u201322.","journal-title":"J Pharmacol Sci"},{"issue":"10","key":"1132_CR33","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.5551\/jat.ER39693","volume":"25","author":"M Sairyo","year":"2018","unstructured":"Sairyo M, Kobayashi T, Masuda D, Kanno K, Zhu Y, Okada T, Koseki M, Ohama T, Nishida M, Sakata Y, et al. A novel selective PPARalpha modulator (SPPARMalpha), K-877 (Pemafibrate), attenuates postprandial hypertriglyceridemia in mice. J Atheroscler Thromb. 2018;25(10):1086.","journal-title":"J Atheroscler Thromb"},{"issue":"1","key":"1132_CR34","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/S0021-9150(98)00141-5","volume":"140","author":"BR Krause","year":"1998","unstructured":"Krause BR, Princen HM. Lack of predictability of classical animal models for hypolipidemic activity: a good time for mice? Atherosclerosis. 1998;140(1):15\u201324.","journal-title":"Atherosclerosis"},{"key":"1132_CR35","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.atherosclerosis.2016.03.003","volume":"249","author":"N Hennuyer","year":"2016","unstructured":"Hennuyer N, Duplan I, Paquet C, Vanhoutte J, Woitrain E, Touche V, Colin S, Vallez E, Lestavel S, Lefebvre P, et al. The novel selective PPARalpha modulator (SPPARMalpha) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis. Atherosclerosis. 2016;249:200\u20138.","journal-title":"Atherosclerosis"},{"key":"1132_CR36","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.atherosclerosis.2017.03.032","volume":"261","author":"Arai H, Yamashita S, Yokote K, Araki E, Suganami H, Ishibashi S, Group KS","year":"2017","unstructured":"Arai H, Yamashita S, Yokote K, Araki E, Suganami H, Ishibashi S, Group KS. Efficacy and safety of K-877, a novel selective peroxisome proliferator-activated receptor alpha modulator (SPPARMalpha), in combination with statin treatment: two randomised, double-blind, placebo-controlled clinical trials in patients with dyslipidaemia. Atherosclerosis. 2017;261:144\u201352.","journal-title":"Atherosclerosis"},{"issue":"6546","key":"1132_CR37","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1038\/377239a0","volume":"377","author":"PL Huang","year":"1995","unstructured":"Huang PL, Huang Z, Mashimo H, Bloch KD, Moskowitz MA, Bevan JA, Fishman MC. Hypertension in mice lacking the gene for endothelial nitric oxide synthase. Nature. 1995;377(6546):239\u201342.","journal-title":"Nature"},{"issue":"6","key":"1132_CR38","doi-asserted-by":"crossref","first-page":"770","DOI":"10.1097\/01.fjc.0000211791.22411.0d","volume":"47","author":"M Saka","year":"2006","unstructured":"Saka M, Obata K, Ichihara S, Cheng XW, Kimata H, Nishizawa T, Noda A, Izawa H, Nagata K, Murohara T, et al. Pitavastatin improves cardiac function and survival in association with suppression of the myocardial endothelin system in a rat model of hypertensive heart failure. J Cardiovasc Pharmacol. 2006;47(6):770\u20139.","journal-title":"J Cardiovasc Pharmacol"},{"issue":"4","key":"1132_CR39","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1159\/000070455","volume":"68","author":"Y Terata","year":"2003","unstructured":"Terata Y, Saito T, Fujiwara Y, Hasegawa H, Miura H, Watanabe H, Chiba Y, Kibira S, Miura M. Pitavastatin inhibits upregulation of intermediate conductance calcium-activated potassium channels and coronary arteriolar remodeling induced by long-term blockade of nitric oxide synthesis. Pharmacology. 2003;68(4):169\u201376.","journal-title":"Pharmacology"},{"issue":"4","key":"1132_CR40","doi-asserted-by":"crossref","first-page":"820","DOI":"10.1097\/HJH.0b013e32835e8227","volume":"31","author":"K Gilbert","year":"2013","unstructured":"Gilbert K, Nian H, Yu C, Luther JM, Brown NJ. Fenofibrate lowers blood pressure in salt-sensitive but not salt-resistant hypertension. J Hypertens. 2013;31(4):820\u20139.","journal-title":"J Hypertens"},{"key":"1132_CR41","doi-asserted-by":"crossref","first-page":"78","DOI":"10.1016\/j.ejphar.2018.09.015","volume":"838","author":"T Dong","year":"2018","unstructured":"Dong T, Lyu J, Imachi H, Kobayashi T, Fukunaga K, Sato S, Ibata T, Yoshimoto T, Yonezaki K, Iwama H, et al. Selective peroxisome proliferator-activated receptor-alpha modulator K-877 regulates the expression of ATP-binding cassette transporter A1 in pancreatic beta cells. Eur J Pharmacol. 2018;838:78\u201384.","journal-title":"Eur J Pharmacol"},{"issue":"9","key":"1132_CR42","doi-asserted-by":"crossref","first-page":"6123","DOI":"10.1074\/jbc.275.9.6123","volume":"275","author":"TJ McCabe","year":"2000","unstructured":"McCabe TJ, Fulton D, Roman LJ, Sessa WC. Enhanced electron flux and reduced calmodulin dissociation may explain \u201ccalcium-independent\u201d eNOS activation by phosphorylation. J Biol Chem. 2000;275(9):6123\u20138.","journal-title":"J Biol Chem"},{"issue":"1","key":"1132_CR43","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1186\/s12933-018-0799-4","volume":"17","author":"J Kim","year":"2018","unstructured":"Kim J, Lee HS, Lee KY. Effect of statins on fasting glucose in non-diabetic individuals: nationwide population-based health examination in Korea. Cardiovasc Diabetol. 2018;17(1):155.","journal-title":"Cardiovasc Diabetol"},{"issue":"1","key":"1132_CR44","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s12933-019-0969-z","volume":"18","author":"HS Jeong","year":"2019","unstructured":"Jeong HS, Hong SJ, Son S, An H, Kook H, Joo HJ, Park JH, Yu CW, Lim DS. Incidence of new-onset diabetes with 1\u00a0mg versus 4\u00a0mg pitavastatin in patients at high risk of developing diabetes during a 3-year follow-up. Cardiovasc Diabetol. 2019;18(1):162.","journal-title":"Cardiovasc Diabetol"},{"key":"1132_CR45","doi-asserted-by":"crossref","unstructured":"Araki M, Nakagawa Y, Oishi A, Han SI, Wang Y, Kumagai K, Ohno H, Mizunoe Y, Iwasaki H, Sekiya M et al: The Peroxisome Proliferator-Activated Receptor alpha (PPARalpha) Agonist Pemafibrate Protects against Diet-Induced Obesity in Mice. Int J Mol Sci 2018, 19(7).","DOI":"10.3390\/ijms19072148"}],"updated-by":[{"DOI":"10.1186\/s12933-020-01181-7","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2020,12,14]],"date-time":"2020-12-14T00:00:00Z","timestamp":1607904000000}}],"container-title":["Cardiovascular Diabetology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-020-01132-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s12933-020-01132-2\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s12933-020-01132-2.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,9,25]],"date-time":"2021-09-25T19:07:04Z","timestamp":1632596824000},"score":1,"resource":{"primary":{"URL":"https:\/\/cardiab.biomedcentral.com\/articles\/10.1186\/s12933-020-01132-2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,26]]},"references-count":45,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2020,12]]}},"alternative-id":["1132"],"URL":"https:\/\/doi.org\/10.1186\/s12933-020-01132-2","relation":{"has-preprint":[{"id-type":"doi","id":"10.21203\/rs.3.rs-20335\/v2","asserted-by":"object"},{"id-type":"doi","id":"10.21203\/rs.3.rs-20335\/v1","asserted-by":"object"}]},"ISSN":["1475-2840"],"issn-type":[{"value":"1475-2840","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,26]]},"assertion":[{"value":"30 March 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 September 2020","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2020","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"14 December 2020","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"An amendment to this paper has been published and can be accessed via the original article.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"All experimental protocols were approved by and conducted in accordance with the recommendations of the Okayama University Animal Care and Use Committee (permit number OKU-2019349).","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"Nakamura K, Miyoshi T, and Ito H received speaker honoraria from Kowa Company, Ltd. The other authors have no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"149"}}