{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T05:56:23Z","timestamp":1782366983391,"version":"3.54.5"},"reference-count":80,"publisher":"Springer Science and Business Media LLC","issue":"12","license":[{"start":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T00:00:00Z","timestamp":1632614400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T00:00:00Z","timestamp":1632614400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"Johannes Kepler University Linz"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Pflugers Arch - Eur J Physiol"],"published-print":{"date-parts":[[2021,12]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In chronic kidney disease (CKD), hyperphosphatemia promotes medial vascular calcification, a process augmented by osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs). VSMC function is regulated by sympathetic innervation, and these cells express \u03b1- and \u03b2-adrenergic receptors. The present study explored the effects of \u03b22-adrenergic stimulation by isoproterenol on VSMC calcification. Experiments were performed in primary human aortic VSMCs treated with isoproterenol during control or high phosphate conditions. As a result, isoproterenol dose dependently up-regulated the expression of osteogenic markers core-binding factor \u03b1-1 (<jats:italic>CBFA1<\/jats:italic>) and tissue-nonspecific alkaline phosphatase (<jats:italic>ALPL<\/jats:italic>) in VSMCs. Furthermore, prolonged isoproterenol exposure augmented phosphate-induced calcification of VSMCs. Isoproterenol increased the activation of PKA and CREB, while knockdown of the PKA catalytic subunit \u03b1 (<jats:italic>PRKACA<\/jats:italic>) or of <jats:italic>CREB1<\/jats:italic> genes was able to suppress the pro-calcific effects of isoproterenol in VSMCs. \u03b22-adrenergic receptor silencing or inhibition with the selective antagonist ICI 118,551 blocked isoproterenol-induced osteogenic signalling in VSMCs. The present observations imply a pro-calcific effect of \u03b22-adrenergic overstimulation in VSMCs, which is mediated, at least partly, by PKA\/CREB signalling. These observations may support a link between sympathetic overactivity in CKD and vascular calcification.<\/jats:p>","DOI":"10.1007\/s00424-021-02621-3","type":"journal-article","created":{"date-parts":[[2021,9,26]],"date-time":"2021-09-26T04:02:40Z","timestamp":1632628960000},"page":"1899-1910","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Increased \u03b2-adrenergic stimulation augments vascular smooth muscle cell calcification via PKA\/CREB signalling"],"prefix":"10.1007","volume":"473","author":[{"given":"Barbara","family":"Moser","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Poetsch","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Misael","family":"Estepa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trang T. D.","family":"Luong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Burkert","family":"Pieske","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Lang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2145-3653","authenticated-orcid":false,"given":"Ioana","family":"Alesutan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jakob","family":"Voelkl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,9,26]]},"reference":[{"key":"2621_CR1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvaa081","author":"I Alesutan","year":"2020","unstructured":"Alesutan I, Luong TTD, Schelski N, Masyout J, Hille S, Schneider MP, Graham D, Zickler D, Verheyen N, Estepa M, Pasch A, Maerz W, Tomaschitz A, Pilz S, Frey N, Lang F, Delles C, Muller OJ, Pieske B, Eckardt KU, Scherberich J, Voelkl J (2020) Circulating uromodulin inhibits vascular calcification by interfering with pro-inflammatory cytokine signaling. Cardiovasc Res. https:\/\/doi.org\/10.1093\/cvr\/cvaa081","journal-title":"Cardiovasc Res"},{"key":"2621_CR2","doi-asserted-by":"publisher","first-page":"523","DOI":"10.1097\/HJH.0000000000001202","volume":"35","author":"I Alesutan","year":"2017","unstructured":"Alesutan I, Tuffaha R, Auer T, Feger M, Pieske B, Lang F, Voelkl J (2017) Inhibition of osteo\/chondrogenic transformation of vascular smooth muscle cells by MgCl2 via calcium-sensing receptor. J Hypertens 35:523\u2013532. https:\/\/doi.org\/10.1097\/HJH.0000000000001202","journal-title":"J Hypertens"},{"key":"2621_CR3","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1038\/s41598-017-01882-2","volume":"7","author":"I Alesutan","year":"2017","unstructured":"Alesutan I, Voelkl J, Feger M, Kratschmar DV, Castor T, Mia S, Sacherer M, Viereck R, Borst O, Leibrock C, Gawaz M, Kuro OM, Pilz S, Tomaschitz A, Odermatt A, Pieske B, Wagner CA, Lang F (2017) Involvement of vascular aldosterone synthase in phosphate-induced osteogenic transformation of vascular smooth muscle cells. Sci Rep 7:2059. https:\/\/doi.org\/10.1038\/s41598-017-01882-2","journal-title":"Sci Rep"},{"key":"2621_CR4","doi-asserted-by":"publisher","first-page":"965","DOI":"10.1186\/1471-2164-15-965","volume":"15","author":"RD Alves","year":"2014","unstructured":"Alves RD, Eijken M, van de Peppel J, van Leeuwen JP (2014) Calcifying vascular smooth muscle cells and osteoblasts: independent cell types exhibiting extracellular matrix and biomineralization-related mimicries. BMC Genomics 15:965. https:\/\/doi.org\/10.1186\/1471-2164-15-965","journal-title":"BMC Genomics"},{"key":"2621_CR5","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1111\/nep.13584","volume":"24","author":"E Arif","year":"2019","unstructured":"Arif E, Nihalani D (2019) Beta2-adrenergic receptor in kidney biology: a current prospective. Nephrology (Carlton) 24:497\u2013503. https:\/\/doi.org\/10.1111\/nep.13584","journal-title":"Nephrology (Carlton)"},{"key":"2621_CR6","doi-asserted-by":"publisher","first-page":"2632","DOI":"10.1074\/jbc.M112.368639","volume":"288","author":"KE Beazley","year":"2013","unstructured":"Beazley KE, Eghtesad S, Nurminskaya MV (2013) Quercetin attenuates warfarin-induced vascular calcification in vitro independently from matrix Gla protein. J Biol Chem 288:2632\u20132640. https:\/\/doi.org\/10.1074\/jbc.M112.368639","journal-title":"J Biol Chem"},{"key":"2621_CR7","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1007\/BF00433772","volume":"362","author":"C Cavallero","year":"1974","unstructured":"Cavallero C, Spagnoli LG, Di Tondo U (1974) Early mitochondrial calcifications in the rabbit aorta after adrenaline. Virchows Arch A Pathol Anat Histol 362:23\u201339. https:\/\/doi.org\/10.1007\/BF00433772","journal-title":"Virchows Arch A Pathol Anat Histol"},{"key":"2621_CR8","doi-asserted-by":"publisher","first-page":"1136","DOI":"10.1177\/1535370213502619","volume":"238","author":"JR Chang","year":"2013","unstructured":"Chang JR, Duan XH, Zhang BH, Teng X, Zhou YB, Liu Y, Yu YR, Zhu Y, Tang CS, Qi YF (2013) Intermedin1-53 attenuates vascular smooth muscle cell calcification by inhibiting endoplasmic reticulum stress via cyclic adenosine monophosphate\/protein kinase A pathway. Exp Biol Med (Maywood) 238:1136\u20131146. https:\/\/doi.org\/10.1177\/1535370213502619","journal-title":"Exp Biol Med (Maywood)"},{"key":"2621_CR9","doi-asserted-by":"publisher","first-page":"1046","DOI":"10.1038\/sj.ki.5001663","volume":"70","author":"NX Chen","year":"2006","unstructured":"Chen NX, Duan D, O\u2019Neill KD, Wolisi GO, Koczman JJ, Laclair R, Moe SM (2006) The mechanisms of uremic serum-induced expression of bone matrix proteins in bovine vascular smooth muscle cells. Kidney Int 70:1046\u20131053. https:\/\/doi.org\/10.1038\/sj.ki.5001663","journal-title":"Kidney Int"},{"key":"2621_CR10","doi-asserted-by":"publisher","first-page":"1172","DOI":"10.1161\/01.res.87.12.1172","volume":"87","author":"A Chesley","year":"2000","unstructured":"Chesley A, Lundberg MS, Asai T, Xiao RP, Ohtani S, Lakatta EG, Crow MT (2000) The beta(2)-adrenergic receptor delivers an antiapoptotic signal to cardiac myocytes through G(i)-dependent coupling to phosphatidylinositol 3\u2019-kinase. Circ Res 87:1172\u20131179. https:\/\/doi.org\/10.1161\/01.res.87.12.1172","journal-title":"Circ Res"},{"key":"2621_CR11","doi-asserted-by":"publisher","first-page":"955","DOI":"10.1124\/mol.60.5.955","volume":"60","author":"A Chruscinski","year":"2001","unstructured":"Chruscinski A, Brede ME, Meinel L, Lohse MJ, Kobilka BK, Hein L (2001) Differential distribution of beta-adrenergic receptor subtypes in blood vessels of knockout mice lacking beta(1)- or beta(2)-adrenergic receptors. Mol Pharmacol 60:955\u2013962. https:\/\/doi.org\/10.1124\/mol.60.5.955","journal-title":"Mol Pharmacol"},{"key":"2621_CR12","doi-asserted-by":"publisher","first-page":"321","DOI":"10.3389\/fphys.2013.00321","volume":"4","author":"V Conti","year":"2013","unstructured":"Conti V, Russomanno G, Corbi G, Izzo V, Vecchione C, Filippelli A (2013) Adrenoreceptors and nitric oxide in the cardiovascular system. Front Physiol 4:321. https:\/\/doi.org\/10.3389\/fphys.2013.00321","journal-title":"Front Physiol"},{"key":"2621_CR13","doi-asserted-by":"publisher","first-page":"1912","DOI":"10.1056\/NEJM199212313272704","volume":"327","author":"RL Converse Jr","year":"1992","unstructured":"Converse RL Jr, Jacobsen TN, Toto RD, Jost CM, Cosentino F, Fouad-Tarazi F, Victor RG (1992) Sympathetic overactivity in patients with chronic renal failure. N Engl J Med 327:1912\u20131918. https:\/\/doi.org\/10.1056\/NEJM199212313272704","journal-title":"N Engl J Med"},{"key":"2621_CR14","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1093\/cvr\/cvs258","volume":"96","author":"RR Cui","year":"2012","unstructured":"Cui RR, Li SJ, Liu LJ, Yi L, Liang QH, Zhu X, Liu GY, Liu Y, Wu SS, Liao XB, Yuan LQ, Mao DA, Liao EY (2012) MicroRNA-204 regulates vascular smooth muscle cell calcification in vitro and in vivo. Cardiovasc Res 96:320\u2013329. https:\/\/doi.org\/10.1093\/cvr\/cvs258","journal-title":"Cardiovasc Res"},{"key":"2621_CR15","doi-asserted-by":"publisher","unstructured":"da Silva RA, da SFG, da CFCJ, Zambuzzi WF (2020) Osteogenic gene markers are epigenetically reprogrammed during contractile-to-calcifying vascular smooth muscle cell phenotype transition. Cell Signal 66:109458. https:\/\/doi.org\/10.1016\/j.cellsig.2019.109458","DOI":"10.1016\/j.cellsig.2019.109458"},{"key":"2621_CR16","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0091877","volume":"9","author":"AP Davel","year":"2014","unstructured":"Davel AP, Brum PC, Rossoni LV (2014) Isoproterenol induces vascular oxidative stress and endothelial dysfunction via a Gialpha-coupled beta2-adrenoceptor signaling pathway. PLoS ONE 9:e91877. https:\/\/doi.org\/10.1371\/journal.pone.0091877","journal-title":"PLoS ONE"},{"key":"2621_CR17","doi-asserted-by":"publisher","first-page":"342","DOI":"10.1159\/000337486","volume":"49","author":"AP Davel","year":"2012","unstructured":"Davel AP, Ceravolo GS, Wenceslau CF, Carvalho MH, Brum PC, Rossoni LV (2012) Increased vascular contractility and oxidative stress in beta(2)-adrenoceptor knockout mice: the role of NADPH oxidase. J Vasc Res 49:342\u2013352. https:\/\/doi.org\/10.1159\/000337486","journal-title":"J Vasc Res"},{"key":"2621_CR18","doi-asserted-by":"publisher","first-page":"H211","DOI":"10.1152\/ajpheart.00581.2007","volume":"295","author":"AP Davel","year":"2008","unstructured":"Davel AP, Fukuda LE, De Sa LL, Munhoz CD, Scavone C, Sanz-Rosa D, Cachofeiro V, Lahera V, Rossoni LV (2008) Effects of isoproterenol treatment for 7 days on inflammatory mediators in the rat aorta. Am J Physiol Heart Circ Physiol 295:H211-219. https:\/\/doi.org\/10.1152\/ajpheart.00581.2007","journal-title":"Am J Physiol Heart Circ Physiol"},{"key":"2621_CR19","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1038\/sj.bjp.0706749","volume":"148","author":"AP Davel","year":"2006","unstructured":"Davel AP, Kawamoto EM, Scavone C, Vassallo DV, Rossoni LV (2006) Changes in vascular reactivity following administration of isoproterenol for 1 week: a role for endothelial modulation. Br J Pharmacol 148:629\u2013639. https:\/\/doi.org\/10.1038\/sj.bjp.0706749","journal-title":"Br J Pharmacol"},{"key":"2621_CR20","doi-asserted-by":"publisher","first-page":"1100","DOI":"10.1161\/CIRCULATIONAHA.119.040232","volume":"140","author":"A de Juan","year":"2019","unstructured":"de Juan A, Ince LM, Pick R, Chen CS, Molica F, Zuchtriegel G, Wang C, Zhang D, Druzd D, Hessenauer MET, Pelli G, Kolbe I, Oster H, Prophete C, Hergenhan SM, Albrecht U, Ripperger J, Montanez E, Reichel CA, Soehnlein O, Kwak BR, Frenette PS, Scheiermann C (2019) Artery-associated sympathetic innervation drives rhythmic vascular inflammation of arteries and veins. Circulation 140:1100\u20131114. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.119.040232","journal-title":"Circulation"},{"key":"2621_CR21","doi-asserted-by":"publisher","first-page":"2938","DOI":"10.1161\/CIRCULATIONAHA.107.743161","volume":"117","author":"LL Demer","year":"2008","unstructured":"Demer LL, Tintut Y (2008) Vascular calcification: pathobiology of a multifaceted disease. Circulation 117:2938\u20132948. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.107.743161","journal-title":"Circulation"},{"key":"2621_CR22","doi-asserted-by":"publisher","first-page":"453","DOI":"10.5604\/12321966.1233567","volume":"24","author":"M Dziedzic","year":"2017","unstructured":"Dziedzic M, Orlowska E, Petkowicz B, Bednarek-Skublewska A, Solski J, Gozdziewska M (2017) Levels of renalase and advanced oxidation protein products with regard to catecholamines in haemodialysed patients. Ann Agric Environ Med 24:453\u2013458. https:\/\/doi.org\/10.5604\/12321966.1233567","journal-title":"Ann Agric Environ Med"},{"key":"2621_CR23","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1016\/S0140-6736(13)60439-0","volume":"382","author":"KU Eckardt","year":"2013","unstructured":"Eckardt KU, Coresh J, Devuyst O, Johnson RJ, Kottgen A, Levey AS, Levin A (2013) Evolving importance of kidney disease: from subspecialty to global health burden. Lancet 382:158\u2013169. https:\/\/doi.org\/10.1016\/S0140-6736(13)60439-0","journal-title":"Lancet"},{"key":"2621_CR24","doi-asserted-by":"publisher","first-page":"1872","DOI":"10.1038\/sj.bjp.0702512","volume":"126","author":"A Ferro","year":"1999","unstructured":"Ferro A, Queen LR, Priest RM, Xu B, Ritter JM, Poston L, Ward JP (1999) Activation of nitric oxide synthase by beta 2-adrenoceptors in human umbilical vein endothelium in vitro. Br J Pharmacol 126:1872\u20131880. https:\/\/doi.org\/10.1038\/sj.bjp.0702512","journal-title":"Br J Pharmacol"},{"key":"2621_CR25","doi-asserted-by":"publisher","first-page":"46","DOI":"10.1097\/MNH.0b013e32834db45d","volume":"21","author":"G Grassi","year":"2012","unstructured":"Grassi G, Bertoli S, Seravalle G (2012) Sympathetic nervous system: role in hypertension and in chronic kidney disease. Curr Opin Nephrol Hypertens 21:46\u201351. https:\/\/doi.org\/10.1097\/MNH.0b013e32834db45d","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2621_CR26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.lfs.2017.12.002","volume":"193","author":"W Hao","year":"2018","unstructured":"Hao W, Yang R, Yang Y, Jin S, Li Y, Yuan F, Guo Q, Xiao L, Wang X, Wang F, Wu Y, Teng X (2018) Stellate ganglion block ameliorates vascular calcification by inhibiting endoplasmic reticulum stress. Life Sci 193:1\u20138. https:\/\/doi.org\/10.1016\/j.lfs.2017.12.002","journal-title":"Life Sci"},{"key":"2621_CR27","doi-asserted-by":"publisher","first-page":"21220","DOI":"10.18632\/aging.103827","volume":"12","author":"F He","year":"2020","unstructured":"He F, Li L, Li PP, Deng Y, Yang YY, Deng YX, Luo HH, Yao XT, Su YX, Gan H, He BC (2020) Cyclooxygenase-2\/sclerostin mediates TGF-beta1-induced calcification in vascular smooth muscle cells and rats undergoing renal failure. Aging (Albany NY) 12:21220\u201321235. https:\/\/doi.org\/10.18632\/aging.103827","journal-title":"Aging (Albany NY)"},{"key":"2621_CR28","doi-asserted-by":"publisher","first-page":"5445","DOI":"10.18632\/aging.102130","volume":"11","author":"LA Henze","year":"2019","unstructured":"Henze LA, Luong TTD, Boehme B, Masyout J, Schneider MP, Brachs S, Lang F, Pieske B, Pasch A, Eckardt KU, Voelkl J, Alesutan I (2019) Impact of C-reactive protein on osteo-\/chondrogenic transdifferentiation and calcification of vascular smooth muscle cells. Aging (Albany NY) 11:5445\u20135462. https:\/\/doi.org\/10.18632\/aging.102130","journal-title":"Aging (Albany NY)"},{"key":"2621_CR29","doi-asserted-by":"publisher","unstructured":"Herrmann J, Babic M, Tolle M, van der Giet M, Schuchardt M (2020) Research models for studying vascular calcification. Int J Mol Sci 21. https:\/\/doi.org\/10.3390\/ijms21062204","DOI":"10.3390\/ijms21062204"},{"key":"2621_CR30","doi-asserted-by":"publisher","first-page":"302","DOI":"10.1016\/j.taap.2013.11.011","volume":"274","author":"JE Herrmann","year":"2014","unstructured":"Herrmann JE, Heale J, Bieraugel M, Ramos M, Fisher RL, Vickers AE (2014) Isoproterenol effects evaluated in heart slices of human and rat in comparison to rat heart in vivo. Toxicol Appl Pharmacol 274:302\u2013312. https:\/\/doi.org\/10.1016\/j.taap.2013.11.011","journal-title":"Toxicol Appl Pharmacol"},{"key":"2621_CR31","doi-asserted-by":"publisher","first-page":"C449","DOI":"10.1152\/ajpcell.00547.2003","volume":"287","author":"DK Hogarth","year":"2004","unstructured":"Hogarth DK, Sandbo N, Taurin S, Kolenko V, Miano JM, Dulin NO (2004) Dual role of PKA in phenotypic modulation of vascular smooth muscle cells by extracellular ATP. Am J Physiol Cell Physiol 287:C449-456. https:\/\/doi.org\/10.1152\/ajpcell.00547.2003","journal-title":"Am J Physiol Cell Physiol"},{"key":"2621_CR32","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1016\/j.febslet.2009.03.039","volume":"583","author":"JJ Hsu","year":"2009","unstructured":"Hsu JJ, Lu J, Huang MS, Geng Y, Sage AP, Bradley MN, Tontonoz P, Demer LL, Tintut Y (2009) T0901317, an LXR agonist, augments PKA-induced vascular cell calcification. FEBS Lett 583:1344\u20131348. https:\/\/doi.org\/10.1016\/j.febslet.2009.03.039","journal-title":"FEBS Lett"},{"key":"2621_CR33","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1016\/j.bbrc.2008.07.062","volume":"374","author":"MS Huang","year":"2008","unstructured":"Huang MS, Sage AP, Lu J, Demer LL, Tintut Y (2008) Phosphate and pyrophosphate mediate PKA-induced vascular cell calcification. Biochem Biophys Res Commun 374:553\u2013558. https:\/\/doi.org\/10.1016\/j.bbrc.2008.07.062","journal-title":"Biochem Biophys Res Commun"},{"key":"2621_CR34","doi-asserted-by":"publisher","first-page":"6","DOI":"10.23876\/j.krcp.18.0143","volume":"38","author":"HS Jang","year":"2019","unstructured":"Jang HS, Kim J, Padanilam BJ (2019) Renal sympathetic nerve activation via alpha2-adrenergic receptors in chronic kidney disease progression. Kidney Res Clin Pract 38:6\u201314. https:\/\/doi.org\/10.23876\/j.krcp.18.0143","journal-title":"Kidney Res Clin Pract"},{"key":"2621_CR35","doi-asserted-by":"publisher","first-page":"12593","DOI":"10.1038\/srep12593","volume":"5","author":"K Jiao","year":"2015","unstructured":"Jiao K, Niu LN, Li QH, Ren GT, Zhao CM, Liu YD, Tay FR, Wang MQ (2015) beta2-Adrenergic signal transduction plays a detrimental role in subchondral bone loss of temporomandibular joint in osteoarthritis. Sci Rep 5:12593. https:\/\/doi.org\/10.1038\/srep12593","journal-title":"Sci Rep"},{"key":"2621_CR36","doi-asserted-by":"publisher","first-page":"883","DOI":"10.1016\/s0741-5214(96)70027-7","volume":"24","author":"BA Jones","year":"1996","unstructured":"Jones BA, Aly HM, Forsyth EA, Sidawy AN (1996) Phenotypic characterization of human smooth muscle cells derived from atherosclerotic tibial and peroneal arteries. J Vasc Surg 24:883\u2013891. https:\/\/doi.org\/10.1016\/s0741-5214(96)70027-7","journal-title":"J Vasc Surg"},{"key":"2621_CR37","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1007\/s00380-013-0427-x","volume":"29","author":"JH Kang","year":"2014","unstructured":"Kang JH, Toita R, Asai D, Yamaoka T, Murata M (2014) Reduction of inorganic phosphate-induced human smooth muscle cells calcification by inhibition of protein kinase A and p38 mitogen-activated protein kinase. Heart Vessels 29:718\u2013722. https:\/\/doi.org\/10.1007\/s00380-013-0427-x","journal-title":"Heart Vessels"},{"key":"2621_CR38","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s13287-016-0335-y","volume":"7","author":"X Ke","year":"2016","unstructured":"Ke X, Shu XR, Wu F, Hu QS, Deng BQ, Wang JF, Nie RQ (2016) Overexpression of the beta2AR gene improves function and re-endothelialization capacity of EPCs after arterial injury in nude mice. Stem Cell Res Ther 7:73. https:\/\/doi.org\/10.1186\/s13287-016-0335-y","journal-title":"Stem Cell Res Ther"},{"key":"2621_CR39","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0043884","volume":"7","author":"HK Kim","year":"2012","unstructured":"Kim HK, Park WS, Warda M, Park SY, Ko EA, Kim MH, Jeong SH, Heo HJ, Choi TH, Hwang YW, Lee SI, Ko KS, Rhee BD, Kim N, Han J (2012) Beta adrenergic overstimulation impaired vascular contractility via actin-cytoskeleton disorganization in rabbit cerebral artery. PLoS ONE 7:e43884. https:\/\/doi.org\/10.1371\/journal.pone.0043884","journal-title":"PLoS ONE"},{"key":"2621_CR40","doi-asserted-by":"publisher","first-page":"1546","DOI":"10.3389\/fphys.2019.01546","volume":"10","author":"MG Kiuchi","year":"2019","unstructured":"Kiuchi MG, Ho JK, Nolde JM, Gavidia LML, Carnagarin R, Matthews VB, Schlaich MP (2019) Sympathetic activation in hypertensive chronic kidney disease - a stimulus for cardiac arrhythmias and sudden cardiac death? Front Physiol 10:1546. https:\/\/doi.org\/10.3389\/fphys.2019.01546","journal-title":"Front Physiol"},{"key":"2621_CR41","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/j.krcp.2015.11.003","volume":"35","author":"MG Kiuchi","year":"2016","unstructured":"Kiuchi MG, Mion D Jr (2016) Chronic kidney disease and risk factors responsible for sudden cardiac death: a whiff of hope? Kidney Res Clin Pract 35:3\u20139. https:\/\/doi.org\/10.1016\/j.krcp.2015.11.003","journal-title":"Kidney Res Clin Pract"},{"key":"2621_CR42","doi-asserted-by":"publisher","first-page":"3239","DOI":"10.1097\/01.asn.0000098687.01005.a5","volume":"14","author":"IH Klein","year":"2003","unstructured":"Klein IH, Ligtenberg G, Neumann J, Oey PL, Koomans HA, Blankestijn PJ (2003) Sympathetic nerve activity is inappropriately increased in chronic renal disease. J Am Soc Nephrol 14:3239\u20133244. https:\/\/doi.org\/10.1097\/01.asn.0000098687.01005.a5","journal-title":"J Am Soc Nephrol"},{"key":"2621_CR43","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1016\/j.bbrc.2016.04.040","volume":"473","author":"GL Lee","year":"2016","unstructured":"Lee GL, Wu JY, Yeh CC, Kuo CC (2016) TLR4 induces CREB-mediated IL-6 production via upregulation of F-spondin to promote vascular smooth muscle cell migration. Biochem Biophys Res Commun 473:1205\u20131210. https:\/\/doi.org\/10.1016\/j.bbrc.2016.04.040","journal-title":"Biochem Biophys Res Commun"},{"key":"2621_CR44","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1007\/s00726-007-0003-8","volume":"34","author":"XB Liao","year":"2008","unstructured":"Liao XB, Zhou XM, Li JM, Yang JF, Tan ZP, Hu ZW, Liu W, Lu Y, Yuan LQ (2008) Taurine inhibits osteoblastic differentiation of vascular smooth muscle cells via the ERK pathway. Amino Acids 34:525\u2013530. https:\/\/doi.org\/10.1007\/s00726-007-0003-8","journal-title":"Amino Acids"},{"key":"2621_CR45","doi-asserted-by":"publisher","first-page":"1731","DOI":"10.1093\/ndt\/gfg414","volume":"18","author":"GM London","year":"2003","unstructured":"London GM, Guerin AP, Marchais SJ, Metivier F, Pannier B, Adda H (2003) Arterial media calcification in end-stage renal disease: impact on all-cause and cardiovascular mortality. Nephrol Dial Transplant 18:1731\u20131740. https:\/\/doi.org\/10.1093\/ndt\/gfg414","journal-title":"Nephrol Dial Transplant"},{"key":"2621_CR46","doi-asserted-by":"publisher","first-page":"663","DOI":"10.3892\/ijmm.2011.631","volume":"27","author":"NC Mackenzie","year":"2011","unstructured":"Mackenzie NC, Zhu D, Longley L, Patterson CS, Kommareddy S, MacRae VE (2011) MOVAS-1 cell line: a new in vitro model of vascular calcification. Int J Mol Med 27:663\u2013668. https:\/\/doi.org\/10.3892\/ijmm.2011.631","journal-title":"Int J Mol Med"},{"key":"2621_CR47","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1152\/physrev.00007.2009","volume":"90","author":"SC Malpas","year":"2010","unstructured":"Malpas SC (2010) Sympathetic nervous system overactivity and its role in the development of cardiovascular disease. Physiol Rev 90:513\u2013557. https:\/\/doi.org\/10.1152\/physrev.00007.2009","journal-title":"Physiol Rev"},{"key":"2621_CR48","doi-asserted-by":"publisher","first-page":"469","DOI":"10.1042\/BJ20131115","volume":"458","author":"S Naqvi","year":"2014","unstructured":"Naqvi S, Martin KJ, Arthur JS (2014) CREB phosphorylation at Ser133 regulates transcription via distinct mechanisms downstream of cAMP and MAPK signalling. Biochem J 458:469\u2013479. https:\/\/doi.org\/10.1042\/BJ20131115","journal-title":"Biochem J"},{"key":"2621_CR49","doi-asserted-by":"publisher","DOI":"10.3791\/54017","author":"C O'Rourke","year":"2016","unstructured":"O\u2019Rourke C, Shelton G, Hutcheson JD, Burke MF, Martyn T, Thayer TE, Shakartzi HR, Buswell MD, Tainsh RE, Yu B, Bagchi A, Rhee DK, Wu C, Derwall M, Buys ES, Yu PB, Bloch KD, Aikawa E, Bloch DB, Malhotra R (2016) Calcification of vascular smooth muscle cells and imaging of aortic calcification and inflammation. J Vis Exp. https:\/\/doi.org\/10.3791\/54017","journal-title":"J Vis Exp"},{"key":"2621_CR50","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2019.108733","volume":"113","author":"BC Oliveira","year":"2019","unstructured":"Oliveira BC, Marques VB, Brun BF, de Oliveira ESHM, Freitas Soares Melo S, Oliveira EM, Dos Santos L, Barauna VG (2019) Dipeptidyl peptidase-4 inhibition prevents vascular dysfunction induced by beta-adrenergic hyperactivity. Biomed Pharmacother 113:108733. https:\/\/doi.org\/10.1016\/j.biopha.2019.108733","journal-title":"Biomed Pharmacother"},{"key":"2621_CR51","doi-asserted-by":"publisher","unstructured":"Opdebeeck B, D'Haese PC, Verhulst A (2020) Molecular and cellular mechanisms that induce arterial calcification by indoxyl sulfate and P-cresyl sulfate. Toxins (Basel) 12. https:\/\/doi.org\/10.3390\/toxins12010058","DOI":"10.3390\/toxins12010058"},{"key":"2621_CR52","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1007\/s10741-007-9007-4","volume":"12","author":"OE Osadchii","year":"2007","unstructured":"Osadchii OE (2007) Cardiac hypertrophy induced by sustained beta-adrenoreceptor activation: pathophysiological aspects. Heart Fail Rev 12:66\u201386. https:\/\/doi.org\/10.1007\/s10741-007-9007-4","journal-title":"Heart Fail Rev"},{"key":"2621_CR53","doi-asserted-by":"publisher","first-page":"I282","DOI":"10.1161\/CIRCULATIONAHA.106.681072","volume":"116","author":"L Osman","year":"2007","unstructured":"Osman L, Chester AH, Sarathchandra P, Latif N, Meng W, Taylor PM, Yacoub MH (2007) A novel role of the sympatho-adrenergic system in regulating valve calcification. Circulation 116:I282-287. https:\/\/doi.org\/10.1161\/CIRCULATIONAHA.106.681072","journal-title":"Circulation"},{"key":"2621_CR54","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1161\/01.res.0000054624.03539.b4","volume":"92","author":"A Remondino","year":"2003","unstructured":"Remondino A, Kwon SH, Communal C, Pimentel DR, Sawyer DB, Singh K, Colucci WS (2003) Beta-adrenergic receptor-stimulated apoptosis in cardiac myocytes is mediated by reactive oxygen species\/c-Jun NH2-terminal kinase-dependent activation of the mitochondrial pathway. Circ Res 92:136\u2013138. https:\/\/doi.org\/10.1161\/01.res.0000054624.03539.b4","journal-title":"Circ Res"},{"key":"2621_CR55","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1007\/s11906-015-0571-z","volume":"17","author":"IM Salman","year":"2015","unstructured":"Salman IM (2015) Cardiovascular autonomic dysfunction in chronic kidney disease: a comprehensive review. Curr Hypertens Rep 17:59. https:\/\/doi.org\/10.1007\/s11906-015-0571-z","journal-title":"Curr Hypertens Rep"},{"key":"2621_CR56","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1007\/s00424-019-02256-5","volume":"471","author":"N Schelski","year":"2019","unstructured":"Schelski N, Luong TTD, Lang F, Pieske B, Voelkl J, Alesutan I (2019) SGK1-dependent stimulation of vascular smooth muscle cell osteo-\/chondrogenic transdifferentiation by interleukin-18. Pflugers Arch 471:889\u2013899. https:\/\/doi.org\/10.1007\/s00424-019-02256-5","journal-title":"Pflugers Arch"},{"key":"2621_CR57","doi-asserted-by":"publisher","DOI":"10.1155\/2012\/915057","volume":"2012","author":"WE Schutzer","year":"2012","unstructured":"Schutzer WE, Mader SL (2012) Biochemical and molecular aspects of vascular adrenergic regulation of blood pressure in the elderly. Int J Hypertens 2012:915057. https:\/\/doi.org\/10.1155\/2012\/915057","journal-title":"Int J Hypertens"},{"key":"2621_CR58","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1016\/j.imr.2014.10.002","volume":"3","author":"E Shin","year":"2014","unstructured":"Shin E, Ko KS, Rhee BD, Han J, Kim N (2014) Different effects of prolonged beta-adrenergic stimulation on heart and cerebral artery. Integr Med Res 3:204\u2013210. https:\/\/doi.org\/10.1016\/j.imr.2014.10.002","journal-title":"Integr Med Res"},{"key":"2621_CR59","doi-asserted-by":"publisher","first-page":"7281","DOI":"10.1073\/pnas.0711190105","volume":"105","author":"R Siddappa","year":"2008","unstructured":"Siddappa R, Martens A, Doorn J, Leusink A, Olivo C, Licht R, van Rijn L, Gaspar C, Fodde R, Janssen F, van Blitterswijk C, de Boer J (2008) cAMP\/PKA pathway activation in human mesenchymal stem cells in vitro results in robust bone formation in vivo. Proc Natl Acad Sci U S A 105:7281\u20137286. https:\/\/doi.org\/10.1073\/pnas.0711190105","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2621_CR60","doi-asserted-by":"publisher","first-page":"1147","DOI":"10.1161\/hh2401.101070","volume":"89","author":"SA Steitz","year":"2001","unstructured":"Steitz SA, Speer MY, Curinga G, Yang HY, Haynes P, Aebersold R, Schinke T, Karsenty G, Giachelli CM (2001) Smooth muscle cell phenotypic transition associated with calcification: upregulation of Cbfa1 and downregulation of smooth muscle lineage markers. Circ Res 89:1147\u20131154. https:\/\/doi.org\/10.1161\/hh2401.101070","journal-title":"Circ Res"},{"key":"2621_CR61","doi-asserted-by":"publisher","unstructured":"Sun Y, Byon CH, Yang Y, Bradley WE, Dell'Italia LJ, Sanders PW, Agarwal A, Wu H, Chen Y (2017) Dietary potassium regulates vascular calcification and arterial stiffness. JCI Insight 2. https:\/\/doi.org\/10.1172\/jci.insight.94920","DOI":"10.1172\/jci.insight.94920"},{"key":"2621_CR62","doi-asserted-by":"publisher","first-page":"543","DOI":"10.1161\/CIRCRESAHA.112.267237","volume":"111","author":"Y Sun","year":"2012","unstructured":"Sun Y, Byon CH, Yuan K, Chen J, Mao X, Heath JM, Javed A, Zhang K, Anderson PG, Chen Y (2012) Smooth muscle cell-specific runx2 deficiency inhibits vascular calcification. Circ Res 111:543\u2013552. https:\/\/doi.org\/10.1161\/CIRCRESAHA.112.267237","journal-title":"Circ Res"},{"key":"2621_CR63","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1111\/j.1440-1681.2005.04222.x","volume":"32","author":"Y Tanaka","year":"2005","unstructured":"Tanaka Y, Horinouchi T, Koike K (2005) New insights into beta-adrenoceptors in smooth muscle: distribution of receptor subtypes and molecular mechanisms triggering muscle relaxation. Clin Exp Pharmacol Physiol 32:503\u2013514. https:\/\/doi.org\/10.1111\/j.1440-1681.2005.04222.x","journal-title":"Clin Exp Pharmacol Physiol"},{"key":"2621_CR64","doi-asserted-by":"publisher","first-page":"572","DOI":"10.1159\/000226225","volume":"46","author":"T Tanikawa","year":"2009","unstructured":"Tanikawa T, Okada Y, Tanikawa R, Tanaka Y (2009) Advanced glycation end products induce calcification of vascular smooth muscle cells through RAGE\/p38 MAPK. J Vasc Res 46:572\u2013580. https:\/\/doi.org\/10.1159\/000226225","journal-title":"J Vasc Res"},{"key":"2621_CR65","doi-asserted-by":"publisher","first-page":"2636","DOI":"10.1161\/01.cir.102.21.2636","volume":"102","author":"Y Tintut","year":"2000","unstructured":"Tintut Y, Patel J, Parhami F, Demer LL (2000) Tumor necrosis factor-alpha promotes in vitro calcification of vascular cells via the cAMP pathway. Circulation 102:2636\u20132642. https:\/\/doi.org\/10.1161\/01.cir.102.21.2636","journal-title":"Circulation"},{"key":"2621_CR66","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1093\/cvr\/cvy023","volume":"114","author":"RM Touyz","year":"2018","unstructured":"Touyz RM, Alves-Lopes R, Rios FJ, Camargo LL, Anagnostopoulou A, Arner A, Montezano AC (2018) Vascular smooth muscle contraction in hypertension. Cardiovasc Res 114:529\u2013539. https:\/\/doi.org\/10.1093\/cvr\/cvy023","journal-title":"Cardiovasc Res"},{"key":"2621_CR67","doi-asserted-by":"publisher","unstructured":"Varennes O, Mentaverri R, Duflot T, Kauffenstein G, Objois T, Lenglet G, Avondo C, Morisseau C, Brazier M, Kamel S, Six I, Bellien J (2020) The metabolism of epoxyeicosatrienoic acids by soluble epoxide hydrolase is protective against the development of vascular calcification. Int J Mol Sci 21. https:\/\/doi.org\/10.3390\/ijms21124313","DOI":"10.3390\/ijms21124313"},{"key":"2621_CR68","doi-asserted-by":"publisher","first-page":"726","DOI":"10.1161\/HYPERTENSIONAHA.116.07911","volume":"68","author":"JA Victorio","year":"2016","unstructured":"Victorio JA, Clerici SP, Palacios R, Alonso MJ, Vassallo DV, Jaffe IZ, Rossoni LV, Davel AP (2016) Spironolactone prevents endothelial nitric oxide synthase uncoupling and vascular dysfunction induced by beta-adrenergic overstimulation: role of perivascular adipose tissue. Hypertension 68:726\u2013735. https:\/\/doi.org\/10.1161\/HYPERTENSIONAHA.116.07911","journal-title":"Hypertension"},{"key":"2621_CR69","doi-asserted-by":"publisher","first-page":"812","DOI":"10.1172\/JCI64093","volume":"123","author":"J Voelkl","year":"2013","unstructured":"Voelkl J, Alesutan I, Leibrock CB, Quintanilla-Martinez L, Kuhn V, Feger M, Mia S, Ahmed MS, Rosenblatt KP, Kuro OM, Lang F (2013) Spironolactone ameliorates PIT1-dependent vascular osteoinduction in klotho-hypomorphic mice. J Clin Invest 123:812\u2013822. https:\/\/doi.org\/10.1172\/JCI64093","journal-title":"J Clin Invest"},{"key":"2621_CR70","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1159\/000430380","volume":"37","author":"J Voelkl","year":"2015","unstructured":"Voelkl J, Castor T, Musculus K, Viereck R, Mia S, Feger M, Alesutan I, Lang F (2015) SGK1-sensitive regulation of cyclin-dependent kinase inhibitor 1b (p27) in cardiomyocyte hypertrophy. Cell Physiol Biochem 37:603\u2013614. https:\/\/doi.org\/10.1159\/000430380","journal-title":"Cell Physiol Biochem"},{"key":"2621_CR71","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1097\/MNH.0000000000000507","volume":"28","author":"J Voelkl","year":"2019","unstructured":"Voelkl J, Cejka D, Alesutan I (2019) An overview of the mechanisms in vascular calcification during chronic kidney disease. Curr Opin Nephrol Hypertens 28:289\u2013296. https:\/\/doi.org\/10.1097\/MNH.0000000000000507","journal-title":"Curr Opin Nephrol Hypertens"},{"key":"2621_CR72","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1042\/CS20190895","volume":"135","author":"J Voelkl","year":"2021","unstructured":"Voelkl J, Egli-Spichtig D, Alesutan I, Wagner CA (2021) Inflammation: a putative link between phosphate metabolism and cardiovascular disease. Clin Sci (Lond) 135:201\u2013227. https:\/\/doi.org\/10.1042\/CS20190895","journal-title":"Clin Sci (Lond)"},{"key":"2621_CR73","doi-asserted-by":"publisher","first-page":"2077","DOI":"10.1007\/s00018-019-03054-z","volume":"76","author":"J Voelkl","year":"2019","unstructured":"Voelkl J, Lang F, Eckardt KU, Amann K, Kuro OM, Pasch A, Pieske B, Alesutan I (2019) Signaling pathways involved in vascular smooth muscle cell calcification during hyperphosphatemia. Cell Mol Life Sci 76:2077\u20132091. https:\/\/doi.org\/10.1007\/s00018-019-03054-z","journal-title":"Cell Mol Life Sci"},{"key":"2621_CR74","doi-asserted-by":"publisher","first-page":"3024","DOI":"10.1172\/JCI96477","volume":"128","author":"J Voelkl","year":"2018","unstructured":"Voelkl J, Luong TT, Tuffaha R, Musculus K, Auer T, Lian X, Daniel C, Zickler D, Boehme B, Sacherer M, Metzler B, Kuhl D, Gollasch M, Amann K, Muller DN, Pieske B, Lang F, Alesutan I (2018) SGK1 induces vascular smooth muscle cell calcification through NF-kappaB signaling. J Clin Invest 128:3024\u20133040. https:\/\/doi.org\/10.1172\/JCI96477","journal-title":"J Clin Invest"},{"key":"2621_CR75","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1681\/ASN.2017050492","volume":"29","author":"J Voelkl","year":"2018","unstructured":"Voelkl J, Tuffaha R, Luong TTD, Zickler D, Masyout J, Feger M, Verheyen N, Blaschke F, Kuro OM, Tomaschitz A, Pilz S, Pasch A, Eckardt KU, Scherberich JE, Lang F, Pieske B, Alesutan I (2018) Zinc inhibits phosphate-induced vascular calcification through TNFAIP3-mediated suppression of NF-kappaB. J Am Soc Nephrol 29:1636\u20131648. https:\/\/doi.org\/10.1681\/ASN.2017050492","journal-title":"J Am Soc Nephrol"},{"key":"2621_CR76","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gng154","volume":"31","author":"X Wang","year":"2003","unstructured":"Wang X, Seed B (2003) A PCR primer bank for quantitative gene expression analysis. Nucleic Acids Res 31:e154. https:\/\/doi.org\/10.1093\/nar\/gng154","journal-title":"Nucleic Acids Res"},{"key":"2621_CR77","doi-asserted-by":"publisher","first-page":"1313","DOI":"10.3389\/fphar.2018.01313","volume":"9","author":"L Wu","year":"2018","unstructured":"Wu L, Tai Y, Hu S, Zhang M, Wang R, Zhou W, Tao J, Han Y, Wang Q, Wei W (2018) Bidirectional role of beta2-adrenergic receptor in autoimmune diseases. Front Pharmacol 9:1313. https:\/\/doi.org\/10.3389\/fphar.2018.01313","journal-title":"Front Pharmacol"},{"key":"2621_CR78","doi-asserted-by":"publisher","first-page":"868","DOI":"10.7150\/ijbs.12045","volume":"11","author":"J Yang","year":"2015","unstructured":"Yang J, Sun H, Zhang J, Hu M, Wang J, Wu G, Wang G (2015) Regulation of beta-adrenergic receptor trafficking and lung microvascular endothelial cell permeability by Rab5 GTPase. Int J Biol Sci 11:868\u2013878. https:\/\/doi.org\/10.7150\/ijbs.12045","journal-title":"Int J Biol Sci"},{"key":"2621_CR79","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2020.583105","volume":"11","author":"W Yu","year":"2020","unstructured":"Yu W, Chen FC, Xu WN, Ding SL, Chen PB, Yang L, Jiang SD, Pan XY (2020) Inhibition of Y1 receptor promotes osteogenesis in bone marrow stromal cells via cAMP\/PKA\/CREB pathway. Front Endocrinol (Lausanne) 11:583105. https:\/\/doi.org\/10.3389\/fendo.2020.583105","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2621_CR80","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1159\/000430376","volume":"37","author":"H Zhang","year":"2015","unstructured":"Zhang H, Li L, Dong Q, Wang Y, Feng Q, Ou X, Zhou P, He T, Luo J (2015) Activation of PKA\/CREB signaling is involved in BMP9-induced osteogenic differentiation of mesenchymal stem cells. Cell Physiol Biochem 37:548\u2013562. https:\/\/doi.org\/10.1159\/000430376","journal-title":"Cell Physiol Biochem"}],"container-title":["Pfl\u00fcgers Archiv - European Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-021-02621-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00424-021-02621-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00424-021-02621-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,17]],"date-time":"2021-11-17T05:07:09Z","timestamp":1637125629000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00424-021-02621-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9,26]]},"references-count":80,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2021,12]]}},"alternative-id":["2621"],"URL":"https:\/\/doi.org\/10.1007\/s00424-021-02621-3","relation":{},"ISSN":["0031-6768","1432-2013"],"issn-type":[{"value":"0031-6768","type":"print"},{"value":"1432-2013","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9,26]]},"assertion":[{"value":"19 January 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"5 August 2021","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"2 September 2021","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 September 2021","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"The authors declare no competing interests.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Conflict of interest"}}]}}