{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T06:11:43Z","timestamp":1787724703917,"version":"build-2784847793"},"reference-count":40,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T00:00:00Z","timestamp":1677715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institute of Health Carlos III (Madrid, Spain)","award":["PI19\/00629"],"award-info":[{"award-number":["PI19\/00629"]}]},{"name":"National Institute of Health Carlos III (Madrid, Spain)","award":["PI19\/00731"],"award-info":[{"award-number":["PI19\/00731"]}]},{"name":"European Union (European Regional Development Fund\u2014ERDF 2014\u20132020)","award":["PI19\/00629"],"award-info":[{"award-number":["PI19\/00629"]}]},{"name":"European Union (European Regional Development Fund\u2014ERDF 2014\u20132020)","award":["PI19\/00731"],"award-info":[{"award-number":["PI19\/00731"]}]},{"name":"Vall d\u2019Hebron Research Institute (VHIR)","award":["PI19\/00629"],"award-info":[{"award-number":["PI19\/00629"]}]},{"name":"Vall d\u2019Hebron Research Institute (VHIR)","award":["PI19\/00731"],"award-info":[{"award-number":["PI19\/00731"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>There is accumulating evidence of autonomic dysfunction in myalgic encephalomyelitis\/chronic fatigue syndrome (ME\/CFS); however, little is known about its association with circadian rhythms and endothelial dysfunction. This study aimed to explore the autonomic responses through an orthostatic test and analysis of the peripheral skin temperature variations and vascular endothelium state in ME\/CFS patients. Sixty-seven adult female ME\/CFS patients and 48 healthy controls were enrolled. Demographic and clinical characteristics were assessed using validated self-reported outcome measures. Postural changes in blood pressure, heart rate, and wrist temperature were recorded during the orthostatic test. Actigraphy during one week was used to determine the 24-h profile of peripheral temperature and activity. Circulating endothelial biomarkers were measured as indicators of endothelial functioning. Results showed that ME\/CFS patients presented higher blood pressure and heart rate values than healthy controls in the supine and standing position (p &lt; 0.05 for both), and also a higher amplitude of the activity rhythm (p &lt; 0.01). Circulating levels of endothelin-1 (ET-1) and vascular cell adhesion molecule-1 (VCAM-1) were significantly higher in ME\/CFS (p &lt; 0.05). In ME\/CFS, ET-1 levels were associated with the stability of the temperature rhythm (p &lt; 0.01), and also with the self-reported questionnaires (p &lt; 0.001). This suggests that ME\/CFS patients exhibited modifications in circadian rhythm and hemodynamic measures, which are associated with endothelial biomarkers (ET-1 and VCAM-1). Future investigation in this area is needed to assess dysautonomia and vascular tone abnormalities, which may provide potential therapeutic targets for ME\/CFS.<\/jats:p>","DOI":"10.3390\/ijms24054835","type":"journal-article","created":{"date-parts":[[2023,3,2]],"date-time":"2023-03-02T03:54:56Z","timestamp":1677729296000},"page":"4835","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Skin Temperature Circadian Rhythms and Dysautonomia in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: The Role of Endothelin-1 in the Vascular Tone Dysregulation"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9009-4690","authenticated-orcid":false,"given":"Trinitat","family":"Cambras","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5615-7961","authenticated-orcid":false,"given":"Maria Fernanda","family":"Zer\u00f3n-Rugerio","sequence":"additional","affiliation":[{"name":"Department of Nutrition, Food Science and Gastronomy, Food Science Torribera Campus, University of Barcelona, 08921 Barcelona, Spain"},{"name":"Nutrition and Food Safety Research Institute, INSA-UB, 08921 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoni","family":"D\u00edez-Noguera","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Physiology, School of Pharmacy and Food Sciences, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9797-0219","authenticated-orcid":false,"given":"Maria Cleof\u00e9","family":"Zaragoz\u00e1","sequence":"additional","affiliation":[{"name":"Clinical Research Department, Laboratorios Vi\u00f1as, 08012 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6356-0836","authenticated-orcid":false,"given":"Joan Carles","family":"Domingo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biomedicine, Faculty of Biology, University of Barcelona, 08028 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramon","family":"Sanmartin-Senta\u00f1es","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, ME\/CFS Clinical Unit, Vall d\u2019Hebron University Hospital, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Division of Rheumatology, ME\/CFS Research Unit, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jose","family":"Alegre-Martin","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, ME\/CFS Clinical Unit, Vall d\u2019Hebron University Hospital, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"},{"name":"Division of Rheumatology, ME\/CFS Research Unit, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2481-3052","authenticated-orcid":false,"given":"Jesus","family":"Castro-Marrero","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, ME\/CFS Research Unit, Vall d\u2019Hebron Research Institute, Universitat Aut\u00f2noma de Barcelona, 08035 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Nacul, L., Authier, F.J., Scheibenbogen, C., Lorusso, L., Helland, I.B., Martin, J.A., Sirbu, C.A., Mengshoel, A.M., Polo, O., and Behrends, U. (2021). European Network on Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome (EUROMENE): Expert Consensus on the Diagnosis, Service Provision, and Care of People with ME\/CFS in Europe. Medicina, 57.","DOI":"10.3390\/medicina57050510"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1111\/bph.13702","article-title":"Treatment and management of chronic fatigue syndrome\/myalgic encephalomyelitis: All roads lead to Rome","volume":"174","author":"Santillo","year":"2017","journal-title":"Br. J. Pharmacol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Cambras, T., Castro-Marrero, J., Zaragoza, M.C., Diez-Noguera, A., and Alegre, J. (2018). Circadian rhythm abnormalities and autonomic dysfunction in patients with Chronic Fatigue Syndrome\/Myalgic Encephalomyelitis. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0198106"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e12703","DOI":"10.1111\/jsr.12703","article-title":"Poor self-reported sleep quality and health-related quality of life in patients with chronic fatigue syndrome\/myalgic encephalomyelitis","volume":"27","author":"Zaragoza","year":"2018","journal-title":"J. Sleep Res."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Cortes Rivera, M., Mastronardi, C., Silva-Aldana, C.T., Arcos-Burgos, M., and Lidbury, B.A. (2019). Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: A Comprehensive Review. Diagnostics, 9.","DOI":"10.3390\/diagnostics9030091"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1007\/s12576-015-0399-y","article-title":"Frontier studies on fatigue, autonomic nerve dysfunction, and sleep-rhythm disorder","volume":"65","author":"Tanaka","year":"2015","journal-title":"J. Physiol. Sci."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1111\/j.1365-2796.2011.02428.x","article-title":"Myalgic encephalomyelitis: International Consensus Criteria","volume":"270","author":"Carruthers","year":"2011","journal-title":"J. Intern. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e17600","DOI":"10.1097\/MD.0000000000017600","article-title":"Evidence of altered cardiac autonomic regulation in myalgic encephalomyelitis\/chronic fatigue syndrome: A systematic review and meta-analysis","volume":"98","author":"Nelson","year":"2019","journal-title":"Medicine"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1056","DOI":"10.1016\/j.jacc.2021.06.045","article-title":"Chronic Fatigue Syndrome and Cardiovascular Disease: JACC State-of-the-Art Review","volume":"78","author":"Natelson","year":"2021","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1186\/s12967-022-03289-8","article-title":"Physiological assessment of orthostatic intolerance in chronic fatigue syndrome","volume":"20","author":"Natelson","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1101","DOI":"10.1001\/jama.2015.1346","article-title":"Beyond myalgic encephalomyelitis\/chronic fatigue syndrome: An IOM report on redefining an illness","volume":"313","author":"Clayton","year":"2015","journal-title":"JAMA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1111\/joim.12564","article-title":"Postural orthostatic tachycardia is not a useful diagnostic marker for chronic fatigue syndrome","volume":"281","author":"Roerink","year":"2017","journal-title":"J. Intern. Med."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"100412","DOI":"10.1016\/j.bbih.2022.100412","article-title":"Circadian rhythm disruption in Myalgic Encephalomyelitis\/Chronic Fatigue Syndrome: Implications for the post-acute sequelae of COVID-19","volume":"20","author":"McCarthy","year":"2022","journal-title":"Brain Behav. Immun. Health"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/B978-0-444-53491-0.00015-8","article-title":"The circadian system and the balance of the autonomic nervous system","volume":"117","author":"Buijs","year":"2013","journal-title":"Handb. Clin. Neurol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Riganello, F., Prada, V., Soddu, A., di Perri, C., and Sannita, W.G. (2019). Circadian Rhythms and Measures of CNS\/Autonomic Interaction. Int. J. Environ. Res. Public Health, 16.","DOI":"10.3390\/ijerph16132336"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/B978-0-12-819975-6.00013-3","article-title":"The circadian system: From clocks to physiology","volume":"179","author":"Buijs","year":"2021","journal-title":"Handb. Clin. Neurol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"S92","DOI":"10.1016\/S0893-133X(01)00315-3","article-title":"Circadian clues to sleep onset mechanisms","volume":"25","author":"Krauchi","year":"2001","journal-title":"Neuropsychopharmacology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"252","DOI":"10.1093\/rheumatology\/keg462","article-title":"Plasma endothelin-1 levels in chronic fatigue syndrome","volume":"43","author":"Kennedy","year":"2004","journal-title":"Rheumatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1186\/s12967-022-03346-2","article-title":"Endothelial dysfunction and altered endothelial biomarkers in patients with post-COVID-19 syndrome and chronic fatigue syndrome (ME\/CFS)","volume":"20","author":"Haffke","year":"2022","journal-title":"J. Transl. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1161\/CIRCRESAHA.109.211706","article-title":"Circadian clocks and vascular function","volume":"106","author":"Paschos","year":"2010","journal-title":"Circ. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1152\/physiol.00021.2020","article-title":"Interplay of the Circadian Clock and Endothelin System","volume":"36","author":"Douma","year":"2021","journal-title":"Physiology"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1186\/s12967-020-02481-y","article-title":"Hemodynamics during the 10-minute NASA Lean Test: Evidence of circulatory decompensation in a subset of ME\/CFS patients","volume":"18","author":"Lee","year":"2020","journal-title":"J. Transl. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1007\/s10286-002-0014-1","article-title":"Hemodynamic and neurohumoral responses to head-up tilt in patients with chronic fatigue syndrome","volume":"12","author":"Timmers","year":"2002","journal-title":"Clin. Auton. Res."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1088\/0967-3334\/33\/2\/231","article-title":"Chronic fatigue syndrome and impaired peripheral pulse characteristics on orthostasis--a new potential diagnostic biomarker","volume":"33","author":"Allen","year":"2012","journal-title":"Physiol. Meas."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Slomko, J., Estevez-Lopez, F., Kujawski, S., Zawadka-Kunikowska, M., Tafil-Klawe, M., Klawe, J.J., Morten, K.J., Szrajda, J., Murovska, M., and Newton, J.L. (2020). Autonomic Phenotypes in Chronic Fatigue Syndrome (CFS) Are Associated with Illness Severity: A Cluster Analysis. J. Clin. Med., 9.","DOI":"10.3390\/jcm9082531"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.jtherbio.2019.01.009","article-title":"Normative surface skin temperature changes due to blood redistribution: A prospective study","volume":"80","author":"Shilco","year":"2019","journal-title":"J. Therm. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.3109\/07420528.2012.719961","article-title":"Diurnal blood pressure variations are associated with changes in distal-proximal skin temperature gradient","volume":"29","author":"Krauchi","year":"2012","journal-title":"Chronobiol. Int."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1017\/S0007114516001884","article-title":"Reversibility of endothelial dysfunction in diabetes: Role of polyphenols","volume":"116","author":"Suganya","year":"2016","journal-title":"Br. J. Nutr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1351","DOI":"10.1016\/j.metabol.2009.12.019","article-title":"Chronic fatigue syndrome is associated with metabolic syndrome: Results from a case-control study in Georgia","volume":"59","author":"Maloney","year":"2010","journal-title":"Metabolism"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"e12663","DOI":"10.1111\/jsr.12663","article-title":"Cardiovascular autonomic dysfunction in insomnia patients with objective short sleep duration","volume":"27","author":"Jarrin","year":"2018","journal-title":"J. Sleep Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1007\/s10286-018-0560-9","article-title":"Autonomic regulation during sleep and wakefulness: A review with implications for defining the pathophysiology of neurological disorders","volume":"28","author":"Fink","year":"2018","journal-title":"Clin. Auton. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"S79","DOI":"10.1093\/clinids\/18.Supplement_1.S79","article-title":"Measuring the functional impact of fatigue: Initial validation of the fatigue impact scale","volume":"18","author":"Fisk","year":"1994","journal-title":"Clin. Infect. Dis."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0165-1781(89)90047-4","article-title":"The Pittsburgh Sleep Quality Index: A new instrument for psychiatric practice and research","volume":"28","author":"Buysse","year":"1989","journal-title":"Psychiatry Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/S0163-8343(03)00043-4","article-title":"A validation study of the hospital anxiety and depression scale (HADS) in a Spanish population","volume":"25","author":"Herrero","year":"2003","journal-title":"Gen. Hosp. Psychiatry"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/j.mayocp.2012.10.013","article-title":"COMPASS 31: A refined and abbreviated Composite Autonomic Symptom Score","volume":"87","author":"Sletten","year":"2012","journal-title":"Mayo. Clin. Proc."},{"key":"ref_36","first-page":"771","article-title":"The Spanish version of the SF-36 Health Survey (the SF-36 health questionnaire): An instrument for measuring clinical results","volume":"104","author":"Alonso","year":"1995","journal-title":"Med. Clin."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"330","DOI":"10.4065\/80.3.330","article-title":"Evaluation of orthostatic hypotension: Relationship of a new self-report instrument to laboratory-based measures","volume":"80","author":"Schrezenmaier","year":"2005","journal-title":"Mayo. Clin. Proc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"102828","DOI":"10.1016\/j.autneu.2021.102828","article-title":"Postural orthostatic tachycardia syndrome (POTS): State of the science and clinical care from a 2019 National Institutes of Health Expert Consensus Meeting\u2014Part 1","volume":"235","author":"Vernino","year":"2021","journal-title":"Auton. Neurosci."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"102836","DOI":"10.1016\/j.autneu.2021.102836","article-title":"Postural orthostatic tachycardia syndrome (POTS): Priorities for POTS care and research from a 2019 National Institutes of Health Expert Consensus Meeting\u2014Part 2","volume":"235","author":"Raj","year":"2021","journal-title":"Auton. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/0166-4328(93)90140-L","article-title":"Non-pharmacological treatment of sleep and wake disturbances in aging and Alzheimer\u2019s disease: Chronobiological perspectives","volume":"57","author":"Mirmiran","year":"1993","journal-title":"Behav. Brain Res."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4835\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T18:45:59Z","timestamp":1760121959000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/5\/4835"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,2]]},"references-count":40,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2023,3]]}},"alternative-id":["ijms24054835"],"URL":"https:\/\/doi.org\/10.3390\/ijms24054835","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,2]]}}}