{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T15:58:00Z","timestamp":1777910280646,"version":"3.51.4"},"reference-count":65,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2014,3,13]],"date-time":"2014-03-13T00:00:00Z","timestamp":1394668800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Physiologica"],"published-print":{"date-parts":[[2014,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Aim<\/jats:title><jats:p>It is unknown how the heart distinguishes various overloads, such as exercise or hypertension, causing either physiological or pathological hypertrophy. We hypothesize that alpha\u2010calcitonin\u2010gene\u2010related peptide (\u03b1<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>), known to be released from contracting skeletal muscles, is key at this remodelling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The hypertrophic effect of \u03b1<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content> was measured <jats:italic>in vitro<\/jats:italic> (cultured cardiac myocytes) and <jats:italic>in vivo<\/jats:italic> (magnetic resonance imaging) in mice. Exercise performance was assessed by determination of maximum oxygen consumption and time to exhaustion. Cardiac phenotype was defined by transcriptional analysis, cardiac histology and morphometry. Finally, we measured spontaneous activity, body fat content, blood volume, haemoglobin mass and skeletal muscle capillarization and fibre composition.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>While \u03b1<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content> exposure yielded larger cultured cardiac myocytes, exercise\u2010induced heart hypertrophy was completely abrogated by treatment with the peptide antagonist <jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>(8\u201037). Exercise performance was attenuated in \u03b1CGRP<jats:sup>\u2212\/\u2212<\/jats:sup> mice or <jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content>(8\u201037) treated wild\u2010type mice but improved in animals with higher density of cardiac CGRP receptors (<jats:styled-content style=\"fixed-case\">CLR<\/jats:styled-content>\u2010tg). Spontaneous activity, body fat content, blood volume, haemoglobin mass, muscle capillarization and fibre composition were unaffected, whereas heart index and ventricular myocyte volume were reduced in \u03b1<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content><jats:sup>\u2212\/\u2212<\/jats:sup> mice and elevated in <jats:styled-content style=\"fixed-case\">CLR<\/jats:styled-content>\u2010tg. Transcriptional changes seen in \u03b1<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content><jats:sup>\u2212\/\u2212<\/jats:sup> (but not <jats:styled-content style=\"fixed-case\">CLR<\/jats:styled-content>\u2010tg) hearts resembled maladaptive cardiac phenotype.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Alpha\u2010calcitonin\u2010gene\u2010related peptide released by skeletal muscles during exercise is a hitherto unrecognized effector directing the strained heart into physiological instead of pathological adaptation. Thus, \u03b1<jats:styled-content style=\"fixed-case\">CGRP<\/jats:styled-content> agonists might be beneficial in heart failure patients.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apha.12244","type":"journal-article","created":{"date-parts":[[2014,1,30]],"date-time":"2014-01-30T20:44:11Z","timestamp":1391114651000},"page":"107-121","source":"Crossref","is-referenced-by-count":7,"title":["Endogenous \u03b1\u2010calcitonin\u2010gene\u2010related peptide promotes exercise\u2010induced, physiological heart hypertrophy in mice"],"prefix":"10.1111","volume":"211","author":[{"given":"B.","family":"Schuler","sequence":"first","affiliation":[{"name":"Institute of Veterinary Physiology Vetsuisse Faculty University of Z\u00fcrich Z\u00fcrich Switzerland"},{"name":"Department of Physiology, Anatomy and Genetics University of Oxford Oxford UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"G.","family":"Rieger","sequence":"additional","affiliation":[{"name":"Institute of Anatomy University of Bern Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Gubser","sequence":"additional","affiliation":[{"name":"Institute of Anatomy University of Bern Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Arras","sequence":"additional","affiliation":[{"name":"Division of Surgical Research University Hospital Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Gianella","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology Vetsuisse Faculty University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology Vetsuisse Faculty University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Jirkof","sequence":"additional","affiliation":[{"name":"Division of Surgical Research University Hospital Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"N.","family":"Cesarovic","sequence":"additional","affiliation":[{"name":"Division of Surgical Research University Hospital Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Klohs","sequence":"additional","affiliation":[{"name":"Institute for Biomedical Engineering University of Zurich and Swiss Federal Institute of Technology Z\u00fcrich (ETHZ) Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"P.","family":"Jakob","sequence":"additional","affiliation":[{"name":"Institute of Physiology and Cardiovascular Research University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Brock","sequence":"additional","affiliation":[{"name":"Division of Pulmonology University Hospital Z\u00fcrich Z\u00fcrich Switzerland"},{"name":"Z\u00fcrich Center for Integrative Human Physiology (ZIHP) Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"T. A.","family":"Gorr","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology Vetsuisse Faculty University of Z\u00fcrich Z\u00fcrich Switzerland"},{"name":"Clinic IV Division of Pediatric Hematology and Oncology University Medical Center Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"O.","family":"Baum","sequence":"additional","affiliation":[{"name":"Institute of Anatomy University of Bern Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"H.","family":"Hoppeler","sequence":"additional","affiliation":[{"name":"Institute of Anatomy University of Bern Bern Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"V.","family":"Samillan\u2010Soto","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology Vetsuisse Faculty University of Z\u00fcrich Z\u00fcrich Switzerland"},{"name":"Physiology Department Medical School Universidad Alas Peruanas Lima Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M.","family":"Gassmann","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology Vetsuisse Faculty University of Z\u00fcrich Z\u00fcrich Switzerland"},{"name":"Z\u00fcrich Center for Integrative Human Physiology (ZIHP) Z\u00fcrich Switzerland"},{"name":"Universidad Peruana Cayetano Heredia (UPCH) Lima Peru"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J. A.","family":"Fischer","sequence":"additional","affiliation":[{"name":"Former Research Laboratory for Calcium Metabolism Orthopedic University Hospital Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W.","family":"Born","sequence":"additional","affiliation":[{"name":"Former Research Laboratory for Calcium Metabolism Orthopedic University Hospital Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Vogel","sequence":"additional","affiliation":[{"name":"Institute of Veterinary Physiology Vetsuisse Faculty University of Z\u00fcrich Z\u00fcrich Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2014,3,13]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2011.209353"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1985.sp015794"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1995.0231"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(97)01015-X"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.2010.02133.x"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.69.1.116"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00694.2005"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2006.093997"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000065225.18093.E4"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.physiol.69.022405.154749"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2006.07.001"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI116270"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/305534a0"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/0196-9781(87)90117-3"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI33302"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod64.6.1776"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.107.065532"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2012.05.024"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-0115(02)00129-5"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00421-007-0618-1"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(85)91232-6"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M107323200"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/oby.2009.341"},{"key":"e_1_2_7_25_1","doi-asserted-by":"crossref","first-page":"1051","DOI":"10.1242\/jeb.201.8.1051","article-title":"Limits for oxygen and substrate transport in mammals","volume":"201","author":"Hoppeler H.","year":"1998","journal-title":"J Exp Biol"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00588462"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.1999.276.1.R259"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.2.155"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.63.4.726"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1258\/la.2012.012027"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsm.2005.022731"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01144.2007"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000152969.42117.ca"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2009.06747.x"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2281.2001.00307.x"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00292.2004"},{"key":"e_1_2_7_37_1","first-page":"199","article-title":"Effect of static handgrip on plasma adrenomedullin concentration in patients with heart failure and in healthy subjects","volume":"53","author":"Krzeminski K.","year":"2002","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_7_38_1","first-page":"571","article-title":"Effect of prolonged dynamic exercise on plasma adrenomedullin concentration in healthy young men","volume":"57","author":"Krzeminski K.","year":"2006","journal-title":"J Physiol Pharmacol"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00629.2007"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.113.109934"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1475-097X.1996.tb00557.x"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsm.2006.031534"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1177\/33.8.2410480"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1006\/mcne.1999.0767"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/30666"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2011.01774.x"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.ph.45.030183.001305"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0306-4522(85)90156-3"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000109493.05849.14"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M101450200"},{"key":"e_1_2_7_51_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI25397"},{"key":"e_1_2_7_52_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-978955"},{"key":"e_1_2_7_53_1","doi-asserted-by":"crossref","first-page":"4193","DOI":"10.1523\/JNEUROSCI.13-10-04193.1993","article-title":"Differential metabolic and electrical activity in the somatic sensory cortex of juvenile and adult rats","volume":"13","author":"Riddle D.R.","year":"1993","journal-title":"J Neurosci"},{"key":"e_1_2_7_54_1","doi-asserted-by":"publisher","DOI":"10.3109\/10520298709107973"},{"key":"e_1_2_7_55_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-980005"},{"key":"e_1_2_7_56_1","first-page":"33","article-title":"Neurogenic inflammation in human and rodent skin","volume":"16","author":"Schmelz M.","year":"2001","journal-title":"News Physiol Sci"},{"key":"e_1_2_7_57_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0912924107"},{"key":"e_1_2_7_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tips.2011.05.002"},{"key":"e_1_2_7_59_1","doi-asserted-by":"publisher","DOI":"10.1161\/hc4101.097111"},{"key":"e_1_2_7_60_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo-119-1-381"},{"key":"e_1_2_7_61_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.97.11.1062"},{"key":"e_1_2_7_62_1","doi-asserted-by":"publisher","DOI":"10.1139\/H09-013"},{"key":"e_1_2_7_63_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.62.4.757"},{"key":"e_1_2_7_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/27.3.341"},{"key":"e_1_2_7_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.11.004"},{"key":"e_1_2_7_66_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-8993(95)00888-W"}],"container-title":["Acta Physiologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fapha.12244","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/apha.12244","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,5]],"date-time":"2023-10-05T10:36:08Z","timestamp":1696502168000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/apha.12244"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,3,13]]},"references-count":65,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,5]]}},"alternative-id":["10.1111\/apha.12244"],"URL":"https:\/\/doi.org\/10.1111\/apha.12244","archive":["Portico"],"relation":{},"ISSN":["1748-1708","1748-1716"],"issn-type":[{"value":"1748-1708","type":"print"},{"value":"1748-1716","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,3,13]]}}}