{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T19:50:54Z","timestamp":1788292254001,"version":"build-2803163510"},"reference-count":77,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T00:00:00Z","timestamp":1785715200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hull and East Riding Cardiac Trust Fund"},{"name":"Tertiary Education Trust Fund"},{"id":[{"id":"https:\/\/ror.org\/03p8jwd38","id-type":"ROR","asserted-by":"publisher"}]},{"name":"University of Benin"},{"id":[{"id":"https:\/\/ror.org\/00wc07928","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Hull York Medical School, University of Hull, UK"},{"id":[{"id":"https:\/\/ror.org\/04nkhwh30","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100022089","name":"University of Botswana","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100022089","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01encsj80","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>While glucose-driven mitochondrial dysfunction has been proposed to promote vascular dysfunction responsible for saphenous vein graft failure (VGF) following bypass surgery, the impact of type 2 diabetes mellitus (T2DM) on mitochondrial function in human saphenous vein smooth muscle cells (HSVSMCs) responsible for maladaptive remodelling is unknown. Our aim was to identify signalling pathways that mediate any mitochondrial dysfunction in HSVSMCs in vitro and assess the impact of T2DM. HSVSMCs explanted from surplus HSV tissues from consenting T2DM and non-diabetic patients undergoing coronary artery bypass graft surgery were treated with known activators and inhibitors of the JAK\/STAT and MAPK\/ERK pathways. Following this, real-time oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) measures of mitochondrial function were then determined. Our findings revealed that both IL-6\/sIL-6R\u03b1 trans-signalling complexes and platelet-derived growth factor-BB (PDGF-BB) significantly increased OCR in HSVSMCs from T2DM patients but not non-diabetic controls. Meanwhile, only PDGF-BB increased ECAR in HSVSMCs from T2DM patients but not in non-diabetic controls. The observed increases in OCR and ECAR were abolished by JAK1\/2-selective inhibitor ruxolitinib. Furthermore, thrombin caused a significant increase in OCR, specifically in HSVSMCs from T2DM patients, and this effect was abolished by the MEK1\/2-selective inhibitor trametinib. Both ruxolitinib and trametinib significantly reduced basal OCR and ECAR in HSVSMCs from both T2DM and non-diabetic patients. Together, these findings demonstrate a JAK\/STAT- and MAPK\/ERK-mediated regulation of mitochondrial function in HSVSMCs. As such, they represent potential targets for regulation of HSVSMC function that can be explored for drug development to limit saphenous VGF in T2DM.<\/jats:p>","DOI":"10.3390\/cells15151402","type":"journal-article","created":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T12:57:56Z","timestamp":1785761876000},"page":"1402","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["JAK and MEK Pathway Regulation of Mitochondrial Activity as Possible Targets for Saphenous Vein Smooth Muscle Cell Dysfunction in Diabetes"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4638-6522","authenticated-orcid":false,"given":"Israel O.","family":"Bolanle","sequence":"first","affiliation":[{"name":"Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, University of Hull, Hull HU6 7RX, UK"},{"name":"Department of Bioengineering, Imperial College London, London SW7 2AZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1399-4943","authenticated-orcid":false,"given":"Florah T.","family":"Moshapa","sequence":"additional","affiliation":[{"name":"School of Pharmacy and Medical Sciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK"},{"name":"School of Pharmacy, Faculty of Health Sciences, University of Botswana, Gaborone P\/Bag-0022, Botswana"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gillian A.","family":"Durham","sequence":"additional","affiliation":[{"name":"Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, University of Hull, Hull HU6 7RX, UK"},{"name":"Pears Cumbria School of Medicine, University of Cumbria, Carlisle CA1 2HH, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James P.","family":"Hobkirk","sequence":"additional","affiliation":[{"name":"School of Sport Exercise and Rehabilitation Sciences, University of Hull, Hull HU6 7RX, UK"},{"name":"School of Cardiovascular & Metabolic Health, British Heart Foundation Glasgow Cardiovascular Research Centre, University of Glasgow, Glasgow G12 8TA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8258-1512","authenticated-orcid":false,"given":"Kirsten","family":"Riches-Suman","sequence":"additional","affiliation":[{"name":"School of Chemistry and Biosciences, Faculty of Life Sciences, University of Bradford, Bradford BD7 1DP, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1826-6686","authenticated-orcid":false,"given":"Mahmoud","family":"Loubani","sequence":"additional","affiliation":[{"name":"Department of Cardiothoracic Surgery, Castle Hill Hospital, Cottingham HU16 5JQ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4423-5058","authenticated-orcid":false,"given":"Roger G.","family":"Sturmey","sequence":"additional","affiliation":[{"name":"Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, University of Hull, Hull HU6 7RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9803-7164","authenticated-orcid":false,"given":"Timothy M.","family":"Palmer","sequence":"additional","affiliation":[{"name":"Biomedical Institute for Multimorbidity, Centre for Biomedicine, Hull York Medical School, University of Hull, Hull HU6 7RX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/nrm.2017.22","article-title":"Protein O-GlcNAcylation: Emerging mechanisms and functions","volume":"18","author":"Yang","year":"2017","journal-title":"Nat. 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