{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T20:32:04Z","timestamp":1792096324945,"version":"4.4.0"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T00:00:00Z","timestamp":1679529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004901","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de Minas Gerais","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004901","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:p>\n                    Pulmonary arterial hypertension is associated with skeletal muscle myopathy and atrophy and impaired exercise tolerance. Aerobic exercise training has been recommended as a non-pharmacological therapy for deleterious effects imposed by pulmonary arterial hypertension. Aerobic physical training induces skeletal muscle adaptations\n                    <jats:italic>via<\/jats:italic>\n                    reduced inflammation, improved anabolic processes, decreased hypoxia and regulation of mitochondrial function. These benefits improve physical exertion tolerance and quality of life in patients with pulmonary arterial hypertension. However, the mechanisms underlying the therapeutic potential of aerobic exercise to skeletal muscle disfunctions in patients with pulmonary arterial hypertension are not well understood yet. This minireview highlights the pathways involved in skeletal muscle adaptations to aerobic exercise training in patients with pulmonary arterial hypertension.\n                  <\/jats:p>","DOI":"10.3389\/fphys.2023.1148146","type":"journal-article","created":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T01:06:57Z","timestamp":1679533617000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["Skeletal muscle dysfunctions in pulmonary arterial hypertension: Effects of aerobic exercise training"],"prefix":"10.3389","volume":"14","author":[{"given":"Filipe Rios","family":"Drummond","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luciano Bernardes","family":"Leite","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Denise Coutinho","family":"de Miranda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lucas Rios","family":"Drummond","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor Neiva","family":"Lavorato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Le\u00f4ncio Lopes","family":"Soares","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cl\u00f3vis Andrade","family":"Neves","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ant\u00f4nio Jos\u00e9","family":"Natali","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.jaci.2016.05.011","article-title":"Inflammatory mechanisms in patients with chronic obstructive pulmonary disease","volume":"138","author":"Barnes","year":"2016","journal-title":"J. Allergy Clin. Immunol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1165\/rcmb.2012-0506OC","article-title":"Skeletal muscle dysfunction in idiopathic pulmonary arterial hypertension","volume":"50","author":"Batt","year":"2014","journal-title":"Am. J. Respir. Cell. Mol. Biol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"2366","DOI":"10.1016\/j.rmed.2007.06.014","article-title":"Skeletal muscle dysfunction in patients with idiopathic pulmonary arterial hypertension","volume":"101","author":"Bauer","year":"2007","journal-title":"Respir. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"86","DOI":"10.1038\/nrrheum.2014.193","article-title":"Exercise as an anti-inflammatory therapy for rheumatic diseases\u2014Myokine regulation","volume":"11","author":"Benatti","year":"2015","journal-title":"Nat. Rev. Rheumatol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"E469","DOI":"10.1152\/ajpendo.00204.2014","article-title":"Skeletal muscle atrophy and the E3 ubiquitin ligases MuRF1 and MAFbx\/atrogin-1","volume":"307","author":"Bodine","year":"2014","journal-title":"Am. J. Physiology-Endocrinology Metabolism"},{"key":"B6","doi-asserted-by":"publisher","first-page":"7783","DOI":"10.1074\/jbc.M608602200","article-title":"MAP4K4 gene silencing in human skeletal muscle prevents tumor necrosis factor-\u03b1-induced insulin resistance","volume":"282","author":"Bouzakri","year":"2007","journal-title":"J. Biol. Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"R197","DOI":"10.1152\/ajpregu.00358.2016","article-title":"High-intensity interval training, but not continuous training, reverses right ventricular hypertrophy and dysfunction in a rat model of pulmonary hypertension","volume":"312","author":"Brown","year":"2017","journal-title":"Am. J. Physiology-Regulatory, Integr. Comp. Physiology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"2004146","DOI":"10.1183\/13993003.04146-2020","article-title":"Exercise training in COPD: Muscle O2 transport plasticity","volume":"58","author":"Broxterman","year":"2021","journal-title":"Eur. Respir. J."},{"key":"B9","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1186\/s12890-015-0031-1","article-title":"Exercise training improves physical fitness in patients with pulmonary arterial hypertension: A systematic review and meta-analysis of controlled trials","volume":"15","author":"Buys","year":"2015","journal-title":"BMC Pulm. Med."},{"key":"B10","doi-asserted-by":"publisher","first-page":"e41701","DOI":"10.1371\/journal.pone.0041701","article-title":"Exercise training prevents oxidative stress and ubiquitin-proteasome system overactivity and reverse skeletal muscle atrophy in heart failure","volume":"7","author":"Cunha","year":"2012","journal-title":"PLoS One"},{"key":"B11","doi-asserted-by":"publisher","first-page":"17070","DOI":"10.1074\/jbc.M312021200","article-title":"Tumor necrosis factor alpha produces insulin resistance in skeletal muscle by activation of inhibitor kappaB kinase in a p38 MAPK-dependent manner","volume":"279","author":"De Alvaro","year":"2004","journal-title":"J. Biol. Chem."},{"key":"B12","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1097\/FJC.0000000000000928","article-title":"Continuous aerobic exercise prevents detrimental remodeling and right heart myocyte contraction and calcium cycling dysfunction in pulmonary artery hypertension","volume":"77","author":"De Jesus Silva","year":"2021","journal-title":"J. Cardiovasc. Pharmacol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1183\/09031936.00027909","article-title":"Effects of exercise training in patients with idiopathic pulmonary arterial hypertension","volume":"34","author":"De Man","year":"2009","journal-title":"Eur. Respir. J."},{"key":"B14","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.bbabio.2013.11.002","article-title":"Functional role of mitochondrial respiratory supercomplexes","volume":"1837","author":"Genova","year":"2014","journal-title":"Biochimica Biophysica Acta (BBA)-Bioenergetics"},{"key":"B15","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.pcad.2014.10.001","article-title":"Exercise training in patients with heart disease: Review of beneficial effects and clinical recommendations","volume":"57","author":"Gielen","year":"2015","journal-title":"Prog. Cardiovasc. Dis."},{"key":"B16","doi-asserted-by":"publisher","first-page":"14440","DOI":"10.1073\/pnas.251541198","article-title":"Atrogin-1, a muscle-specific F-box protein highly expressed during muscle atrophy","volume":"98","author":"Gomes","year":"2001","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B17","doi-asserted-by":"publisher","first-page":"107831","DOI":"10.1096\/fasebj.26.1_supplement.1078.31","article-title":"Exercise preconditioning prevents skeletal muscle wasting in monocrotaline\u2010induced cardiac cachexia","volume":"26","author":"Gon\u00e7alves","year":"2012","journal-title":"Physiology"},{"key":"B18","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1161\/CIRCULATIONAHA.108.829713","article-title":"Opposite effects of training in rats with stable and progressive pulmonary hypertension","volume":"120","author":"Handoko","year":"2009","journal-title":"Circulation"},{"key":"B19","doi-asserted-by":"publisher","first-page":"S10","DOI":"10.1016\/j.jacc.2009.04.006","article-title":"Inflammation, growth factors, and pulmonary vascular remodeling","volume":"54","author":"Hassoun","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/j.jacc.2013.10.032","article-title":"Definitions and diagnosis of pulmonary hypertension","volume":"42","author":"Hoeper","year":"2014","journal-title":"Turk Kardiyol. Dernegi arsivi Turk Kardiyol. Derneginin yayin organidir"},{"key":"B21","doi-asserted-by":"publisher","first-page":"a029793","DOI":"10.1101\/cshperspect.a029793","article-title":"Skeletal muscle as an endocrine organ: The role of myokines in exercise adaptations","volume":"7","author":"Hoffmann","year":"2017","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"B22","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/j.ccl.2016.04.005","article-title":"Pulmonary hypertension in children","volume":"34","author":"Ivy","year":"2016","journal-title":"Cardiol. Clin."},{"key":"B23","doi-asserted-by":"publisher","first-page":"432","DOI":"10.1097\/00008483-199811000-00005","article-title":"Chronic obstructive pulmonary disease: Capillarity and fiber-type characteristics of skeletal muscle","volume":"18","author":"Jobin","year":"1998","journal-title":"J. Cardiopulm. Rehabilitation Prev."},{"key":"B24","doi-asserted-by":"publisher","first-page":"475","DOI":"10.1536\/ihj.15-108","article-title":"Skeletal muscle abnormalities in heart failure","volume":"56","author":"Kinugawa","year":"2015","journal-title":"Int. heart J."},{"key":"B25","first-page":"A6768","article-title":"Pulmonary hypertension-induced exercise intolerance is improved with exercise and correlates with expression of skeletal muscle respiratory chain proteins","volume-title":"C98. Hot things: INFLAMMATION, remodeling, and systemic disease in pulmonary hypertension","author":"Kue","year":"2017"},{"key":"B26","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1096\/fj.04-2364com","article-title":"TNF\u2010\u03b1 acts via p38 MAPK to stimulate expression of the ubiquitin ligase atrogin1\/MAFbx in skeletal muscle","volume":"19","author":"Li","year":"2005","journal-title":"FASEB J."},{"key":"B27","doi-asserted-by":"publisher","first-page":"2273","DOI":"10.1249\/MSS.0000000000000696","article-title":"Impaired skeletal muscle oxygenation and exercise tolerance in pulmonary hypertension","volume":"47","author":"Malenfant","year":"2015","journal-title":"Med. Sci. Sports Exerc"},{"key":"B28","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.numecd.2014.10.005","article-title":"Pulmonary arterial hypertension-related myopathy: An overview of current data and future perspectives","volume":"25","author":"Marra","year":"2015","journal-title":"Nutr. Metabolism Cardiovasc. Dis."},{"key":"B29","doi-asserted-by":"publisher","first-page":"104","DOI":"10.3389\/fphys.2014.00104","article-title":"Structural alterations of skeletal muscle in copd","volume":"5","author":"Mathur","year":"2014","journal-title":"Front. physiology"},{"key":"B30","doi-asserted-by":"publisher","first-page":"2045894020925762","DOI":"10.1177\/2045894020925762","article-title":"Endurance exercise training in pulmonary hypertension increases skeletal muscle electron transport chain supercomplex assembly","volume":"10","author":"McCullough","year":"2020","journal-title":"Pulm. Circ."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1016\/j.jacc.2009.01.004","article-title":"ACCF\/AHA 2009 expert consensus document on pulmonary hypertension: A report of the American college of cardiology foundation task force on expert consensus documents and the American heart association developed in collaboration with the American college of chest physicians; American thoracic society, inc.; and the pulmonary hypertension association","volume":"53","author":"McLaughlin","year":"2009","journal-title":"J. Am. Coll. Cardiol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1183\/09031936.04.00095804","article-title":"Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension","volume":"25","author":"Meyer","year":"2005","journal-title":"Eur. Respir. J."},{"key":"B33","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1007\/s00395-015-0514-5","article-title":"Cardioprotective effects of early and late aerobic exercise training in experimental pulmonary arterial hypertension","volume":"110","author":"Moreira-Gon\u00e7alves","year":"","journal-title":"Basic Res. Cardiol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"2722","DOI":"10.1016\/j.bbadis.2015.10.002","article-title":"Signaling pathways underlying skeletal muscle wasting in experimental pulmonary arterial hypertension","volume":"1852","author":"Moreira-Gon\u00e7alves","year":"","journal-title":"Biochimica Biophysica Acta (BBA)-Molecular Basis Dis."},{"key":"B35","doi-asserted-by":"publisher","first-page":"H421","DOI":"10.1152\/ajpheart.00262.2015","article-title":"Voluntary exercise delays heart failure onset in rats with pulmonary artery hypertension","volume":"309","author":"Natali","year":"2015","journal-title":"Am. J. Physiology-Heart Circulatory Physiology"},{"key":"B36","doi-asserted-by":"publisher","first-page":"70","DOI":"10.1016\/j.rmed.2017.11.022","article-title":"Mechanisms underlying the impact of exercise training in pulmonary arterial hypertension","volume":"134","author":"Nogueira-Ferreira","year":"2018","journal-title":"Respir. Med."},{"key":"B37","doi-asserted-by":"publisher","first-page":"172","DOI":"10.1126\/science.1230721","article-title":"Pleiotropic actions of insulin resistance and inflammation in metabolic homeostasis","volume":"339","author":"Odegaard","year":"2013","journal-title":"Science"},{"key":"B38","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrendo.2012.49","article-title":"Muscles, exercise and obesity: Skeletal muscle as a secretory organ","volume":"8","author":"Pedersen","year":"2012","journal-title":"Nat. Rev. Endocrinol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/sms.12581","article-title":"Exercise as medicine\u2013evidence for prescribing exercise as therapy in 26 different chronic diseases","volume":"25","author":"Pedersen","year":"2015","journal-title":"Scand. J. Med. Sci. sports"},{"key":"B40","doi-asserted-by":"publisher","first-page":"410","DOI":"10.3390\/jcm9020410","article-title":"Skeletal and respiratory muscle dysfunctions in pulmonary arterial hypertension","volume":"9","author":"Riou","year":"2020","journal-title":"J. Clin. Med."},{"key":"B41","doi-asserted-by":"publisher","first-page":"45777","DOI":"10.1074\/jbc.M301977200","article-title":"Interleukin-6 (IL-6) induces insulin resistance in 3T3-L1 adipocytes and is, like IL-8 and tumor necrosis factor-\u03b1, overexpressed in human fat cells from insulin-resistant subjects","volume":"278","author":"Rotter","year":"2003","journal-title":"J. Biol. Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"391","DOI":"10.1016\/j.cjca.2015.01.023","article-title":"Right ventricular adaptation and failure in pulmonary arterial hypertension","volume":"31","author":"Ryan","year":"2015","journal-title":"Can. J. Cardiol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"565","DOI":"10.1016\/j.rec.2018.02.002","article-title":"Interventional therapies in pulmonary hypertension","volume":"71","author":"Sandoval","year":"2018","journal-title":"Rev. Espa\u00f1ola Cardiol. (English Ed."},{"key":"B44","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1152\/physiol.00041.2007","article-title":"Signaling in muscle atrophy and hypertrophy","volume":"23","author":"Sandri","year":"2008","journal-title":"Physiology"},{"key":"B45","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1097\/01823246-200920040-00003","article-title":"Exercise training in patients with pulmonary arterial hypertension: A case report","volume":"20","author":"Shoemaker","year":"2009","journal-title":"Cardiopulm. Phys. Ther. J."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1801913","DOI":"10.1183\/13993003.01913-2018","article-title":"Haemodynamic definitions and updated clinical classification of pulmonary hypertension","volume":"53","author":"Simonneau","year":"2019","journal-title":"Eur. Respir. J."},{"key":"B47","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1016\/j.scispo.2018.02.012","article-title":"Exercise training and pulmonary arterial hypertension: A review of the cardiac benefits","volume":"33","author":"Soares","year":"2018","journal-title":"Sci. Sports"},{"key":"B48","doi-asserted-by":"publisher","first-page":"116974","DOI":"10.1016\/j.lfs.2019.116974","article-title":"Voluntary running counteracts right ventricular adverse remodeling and myocyte contraction impairment in pulmonary arterial hypertension model","volume":"238","author":"Soares","year":"2019","journal-title":"Life Sci."},{"key":"B49","doi-asserted-by":"publisher","first-page":"920","DOI":"10.1161\/CIRCULATIONAHA.109.933762","article-title":"Elevated levels of inflammatory cytokines predict survival in idiopathic and familial pulmonary arterial hypertension","volume":"122","author":"Soon","year":"2010","journal-title":"Circulation"},{"key":"B50","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1111\/j.1440-1681.2008.04936.x","article-title":"Effects of a chronic exercise training protocol on oxidative stress and right ventricular hypertrophy in monocrotaline\u2010treated rats","volume":"35","author":"Souza\u2010Rabbo","year":"2008","journal-title":"Clin. Exp. Pharmacol. Physiology"},{"key":"B51","doi-asserted-by":"publisher","first-page":"E433","DOI":"10.1152\/ajpendo.00074.2003","article-title":"IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans","volume":"285","author":"Steensberg","year":"2003","journal-title":"Am. J. Physiology-Endocrinology Metabolism"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1113\/EP088105","article-title":"Exercise intolerance in heart failure: The important role of pulmonary hypertension","volume":"105","author":"Taylor","year":"2020","journal-title":"Exp. Physiol."},{"key":"B53","doi-asserted-by":"publisher","first-page":"148","DOI":"10.1111\/resp.13141","article-title":"Pathophysiology of exercise intolerance in pulmonary arterial hypertension","volume":"23","author":"Tran","year":"2018","journal-title":"Respirology"},{"key":"B54","doi-asserted-by":"publisher","first-page":"118298","DOI":"10.1016\/j.lfs.2020.118298","article-title":"Exercise intolerance establishment in pulmonary hypertension: Preventive effect of aerobic exercise training","volume":"261","author":"Vieira","year":"2020","journal-title":"Life Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1007\/s12020-012-9725-9","article-title":"Testosterone and heart failure","volume":"42","author":"Volterrani","year":"2012","journal-title":"Endocrine"},{"key":"B56","doi-asserted-by":"publisher","first-page":"R673","DOI":"10.1152\/ajpregu.00561.2007","article-title":"Skeletal muscle insulin resistance: Role of inflammatory cytokines and reactive oxygen species","volume":"294","author":"Wei","year":"2008","journal-title":"Am. J. Physiology-Regulatory, Integr. Comp. Physiology"},{"key":"B57","doi-asserted-by":"publisher","first-page":"7060","DOI":"10.1074\/jbc.M509782200","article-title":"Direct cross-talk of interleukin-6 and insulin signal transduction via insulin receptor substrate-1 in skeletal muscle cells","volume":"281","author":"Weigert","year":"2006","journal-title":"J. Biol. Chem."},{"key":"B58","doi-asserted-by":"publisher","first-page":"28","DOI":"10.12688\/f1000research.14984.1","article-title":"Recent advances in pulmonary arterial hypertension","volume":"11","author":"Wilkins","year":"2018","journal-title":"F1000Res."},{"key":"B59","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1097\/MAJ.0000000000000511","article-title":"Mechanisms of cachexia in chronic disease states","volume":"350","author":"Yoshida","year":"2015","journal-title":"Am. J. Med. Sci."},{"key":"B60","doi-asserted-by":"publisher","first-page":"214","DOI":"10.5114\/aoms.2018.81037","article-title":"BDNF contributes to the skeletal muscle anti-atrophic effect of exercise training through AMPK-PGC1\u03b1 signaling in heart failure mice","volume":"15","author":"Zhang","year":"2019","journal-title":"Archives Med. Sci."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1148146\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,23]],"date-time":"2023-03-23T01:07:00Z","timestamp":1679533620000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphys.2023.1148146\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,23]]},"references-count":60,"alternative-id":["10.3389\/fphys.2023.1148146"],"URL":"https:\/\/doi.org\/10.3389\/fphys.2023.1148146","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,23]]},"article-number":"1148146"}}