{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T14:39:44Z","timestamp":1790433584096,"version":"4.1.0"},"reference-count":106,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T00:00:00Z","timestamp":1702425600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Health and Medical Research Council","award":["NHMRC APP1188218"],"award-info":[{"award-number":["NHMRC APP1188218"]}]},{"name":"NHMRC","award":["NHMRC APP1188218"],"award-info":[{"award-number":["NHMRC APP1188218"]}]},{"name":"MRFF Queensland Government","award":["NHMRC APP1188218"],"award-info":[{"award-number":["NHMRC APP1188218"]}]},{"name":"Heart Foundation","award":["NHMRC APP1188218"],"award-info":[{"award-number":["NHMRC APP1188218"]}]},{"name":"Vascular Foundation","award":["NHMRC APP1188218"],"award-info":[{"award-number":["NHMRC APP1188218"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Peripheral artery disease (PAD) is caused by blocked arteries due to atherosclerosis and\/or thrombosis which reduce blood flow to the lower limbs. It results in major morbidity, including ischemic limb, claudication, and amputation, with patients also suffering a heightened risk of heart attack, stroke, and death. Recent studies suggest women have a higher prevalence of PAD than men, and with worse outcomes after intervention. In addition to a potential unconscious bias faced by women with PAD in the health system, with underdiagnosis, and lower rates of guideline-based therapy, fundamental biological differences between men and women may be important. In this review, we highlight sexual dimorphisms in endothelial cell functions and how they may impact PAD pathophysiology in women. Understanding sex-specific mechanisms in PAD is essential for the development of new therapies and personalized care for patients with PAD.<\/jats:p>","DOI":"10.3390\/ijms242417439","type":"journal-article","created":{"date-parts":[[2023,12,13]],"date-time":"2023-12-13T08:55:16Z","timestamp":1702457716000},"page":"17439","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Sex, Endothelial Cell Functions, and Peripheral Artery Disease"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1723-2679","authenticated-orcid":false,"given":"Si\u00e2n P.","family":"Cartland","sequence":"first","affiliation":[{"name":"Heart Research Institute, The University of Sydney, Sydney, NSW 2042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher P.","family":"Stanley","sequence":"additional","affiliation":[{"name":"Heart Research Institute, The University of Sydney, Sydney, NSW 2042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0682-8760","authenticated-orcid":false,"given":"Christina","family":"Bursill","sequence":"additional","affiliation":[{"name":"South Australian Health and Medical Research Institute, Adelaide, SA 5000, Australia"},{"name":"Adelaide Medical School, University of Adelaide, Adelaide, SA 5005, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4584-2044","authenticated-orcid":false,"given":"Freda","family":"Passam","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medicine, The University of Sydney, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gemma A.","family":"Figtree","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medicine, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Kolling Institute of Medical Research, Sydney, NSW 2064, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sanjay","family":"Patel","sequence":"additional","affiliation":[{"name":"Heart Research Institute, The University of Sydney, Sydney, NSW 2042, Australia"},{"name":"Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacky","family":"Loa","sequence":"additional","affiliation":[{"name":"Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5779-8848","authenticated-orcid":false,"given":"Jonathan","family":"Golledge","sequence":"additional","affiliation":[{"name":"Queensland Research Centre for Peripheral Vascular Disease, College of Medicine and Dentistry, James Cook University, Townsville, QLD 4811, Australia"},{"name":"Department of Vascular and Endovascular Surgery, The Townsville University Hospital, Townsville, QLD 4814, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David A.","family":"Robinson","sequence":"additional","affiliation":[{"name":"Royal Prince Alfred Hospital, Sydney, NSW 2050, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Aitken","sequence":"additional","affiliation":[{"name":"Faculty of Health and Medicine, The University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Concord Institute of Academic Surgery, Concord Repatriation General Hospital, Sydney, NSW 2139, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary M.","family":"Kavurma","sequence":"additional","affiliation":[{"name":"Heart Research Institute, The University of Sydney, Sydney, NSW 2042, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e171","DOI":"10.1161\/CIR.0000000000001005","article-title":"Lower Extremity Peripheral Artery Disease: Contemporary Epidemiology, Management Gaps, and Future Directions: A Scientific Statement From the American Heart Association","volume":"144","author":"Criqui","year":"2021","journal-title":"Circulation"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"107843","DOI":"10.1016\/j.diabres.2019.107843","article-title":"Global and regional diabetes prevalence estimates for 2019 and projections for 2030 and 2045: Results from the International Diabetes Federation Diabetes Atlas, 9(th) edition","volume":"157","author":"Saeedi","year":"2019","journal-title":"Diabetes Res. Clin. Prac."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1016\/j.apmr.2007.11.005","article-title":"Estimating the Prevalence of Limb Loss in the United States: 2005 to 2050","volume":"89","author":"MacKenzie","year":"2008","journal-title":"Arch. Phys. Med. Rehabil."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"239","DOI":"10.31128\/AJGP-11-19-5160","article-title":"Peripheral artery disease in the lower limbs: The importance of secondary risk prevention for improved long-term prognosis","volume":"49","author":"Aitken","year":"2022","journal-title":"Am. J. Gen. Pract."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"489","DOI":"10.7547\/0980489","article-title":"Mortality rates and diabetic foot ulcers: Is it time to communicate mortality risk to patients with diabetic foot ulceration?","volume":"98","author":"Robbins","year":"2008","journal-title":"J. Am. Podiatr. Med. Assoc."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1808","DOI":"10.1161\/ATVBAHA.120.314595","article-title":"Epidemiology and Risk of Amputation in Patients with Diabetes Mellitus and Peripheral Artery Disease","volume":"40","author":"Barnes","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1185","DOI":"10.1016\/j.jvs.2007.02.004","article-title":"A population-based study of peripheral arterial disease prevalence with special focus on critical limb ischemia and sex differences","volume":"45","author":"Sigvant","year":"2007","journal-title":"J. Vasc. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1002\/ccd.21969","article-title":"Prevalence and prediction of previously unrecognized peripheral arterial disease in patients with coronary artery disease: The Peripheral Arterial Disease in Interventional Patients Study","volume":"73","author":"Moussa","year":"2009","journal-title":"Catheter. Cardiovasc. Interv."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/S0021-9150(03)00204-1","article-title":"High prevalence of peripheral arterial disease and co-morbidity in 6880 primary care patients: Cross-sectional study","volume":"172","author":"Diehm","year":"2004","journal-title":"Atherosclerosis"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1161\/01.CIR.101.9.1007","article-title":"Asymptomatic peripheral arterial disease is independently associated with impaired lower extremity functioning: The women\u2019s health and aging study","volume":"101","author":"McDermott","year":"2000","journal-title":"Circulation"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7475","DOI":"10.1073\/pnas.92.16.7475","article-title":"An antiestrogen: A phosphotyrosyl peptide that blocks dimerization of the human estrogen receptor","volume":"92","author":"Arnold","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1161\/CIRCRESAHA.121.320702","article-title":"Sex Differences in Peripheral Artery Disease","volume":"130","author":"Pabon","year":"2022","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e010849","DOI":"10.1161\/JAHA.118.010849","article-title":"Sex Differences in Outcomes Following Endovascular Treatment for Symptomatic Peripheral Artery Disease: An Analysis From the K- VIS ELLA Registry","volume":"8","author":"Choi","year":"2019","journal-title":"J. Am. Heart Assoc."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1177\/1358863X14565373","article-title":"The persistence of gender and racial disparities in vascular lower extremity amputation: An examination of HCUP-NIS data (2002-2011)","volume":"20","author":"Lefebvre","year":"2015","journal-title":"Vasc. Med."},{"key":"ref_15","first-page":"342","article-title":"A hidden problem: Peripheral artery disease in women","volume":"9","author":"Kavurma","year":"2023","journal-title":"Eur. Heart J. Qual. Care Clin. Outcomes"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1054576","DOI":"10.3389\/fcvm.2022.1054576","article-title":"Endothelial cell dysfunction: Implications for the pathogenesis of peripheral artery disease","volume":"9","author":"Kavurma","year":"2022","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1982","DOI":"10.1161\/ATVBAHA.119.312864","article-title":"Pathologic Disparities between Peripheral Artery Disease and Coronary Artery Disease","volume":"40","author":"Narula","year":"2020","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2152","DOI":"10.1016\/j.jacc.2018.08.002","article-title":"Pathology of Peripheral Artery Disease in Patients with Critical Limb Ischemia","volume":"72","author":"Narula","year":"2018","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1001\/jama.295.12.1420","article-title":"Sex differences in platelet reactivity and response to low-dose aspirin therapy","volume":"295","author":"Becker","year":"2006","journal-title":"JAMA"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1016\/j.atherosclerosis.2015.01.017","article-title":"Sex differences in coronary artery disease: Pathological observations","volume":"239","author":"Yahagi","year":"2015","journal-title":"Atherosclerosis"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/0735-1097(94)90305-0","article-title":"Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women","volume":"24","author":"Celermajer","year":"1994","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"H1499","DOI":"10.1152\/ajpheart.00194.2018","article-title":"Sex differences in the vascular function and related mechanisms: Role of 17beta-estradiol","volume":"315","author":"Pabbidi","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/bs.apha.2016.05.003","article-title":"Estrogens and Coronary Artery Disease: New Clinical Perspectives","volume":"77","author":"Meyer","year":"2016","journal-title":"Adv. Pharmacol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"H1569","DOI":"10.1152\/ajpheart.00396.2018","article-title":"Sex differences in endothelial function important to vascular health and overall cardiovascular disease risk across the lifespan","volume":"315","author":"Stanhewicz","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"H2027","DOI":"10.1152\/ajpheart.00004.2011","article-title":"Gender differences affect blood flow recovery in a mouse model of hindlimb ischemia","volume":"300","author":"Peng","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2068","DOI":"10.1161\/01.CIR.95.8.2068","article-title":"Biochemical evidence for impaired nitric oxide synthesis in patients with peripheral arterial occlusive disease","volume":"95","author":"Boger","year":"1997","journal-title":"Circulation"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10003","DOI":"10.1038\/srep10003","article-title":"The Association between Serum Uric Acid Levels and the Prevalence of Vulnerable Atherosclerotic Carotid Plaque: A Cross-sectional Study","volume":"5","author":"Li","year":"2015","journal-title":"Sci. Rep."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Lee, T.S., Lu, T.M., Chen, C.H., Guo, B.C., and Hsu, C.P. (2021). Hyperuricemia induces endothelial dysfunction and accelerates atherosclerosis by disturbing the asymmetric dimethylarginine\/dimethylarginine dimethylaminotransferase 2 pathway. Redox. Biol., 46.","DOI":"10.1016\/j.redox.2021.102108"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.ceca.2012.01.003","article-title":"Hyperuricemia induces endothelial dysfunction via mitochondrial Na+\/Ca2+ exchanger-mediated mitochondrial calcium overload","volume":"51","author":"Hong","year":"2012","journal-title":"Cell Calcium"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.atherosclerosis.2019.07.013","article-title":"Elevated serum uric acid is associated with peripheral endothelial dysfunction in women","volume":"290","author":"Taher","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ejphar.2008.10.042","article-title":"Effects of a Western diet versus high glucose on endothelium-dependent relaxation in murine micro- and macro-vasculature","volume":"601","author":"Ellis","year":"2008","journal-title":"Eur. J. Pharmacol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1038\/sj.bjp.0705549","article-title":"Catalase has negligible inhibitory effects on endothelium-dependent relaxations in mouse isolated aorta and small mesenteric artery","volume":"140","author":"Ellis","year":"2003","journal-title":"Br. J. Pharmacol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1161\/hh0402.105096","article-title":"Estradiol alters nitric oxide production in the mouse aorta through the alpha-, but not beta-, estrogen receptor","volume":"90","author":"Darblade","year":"2002","journal-title":"Circ. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"H725","DOI":"10.1152\/ajpheart.00696.2009","article-title":"Role of arachidonic acid lipoxygenase metabolites in acetylcholine-induced relaxations of mouse arteries","volume":"300","author":"Gauthier","year":"2011","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/S0014-2999(00)00619-1","article-title":"Heterogeneity in relaxation mechanisms in the carotid and the femoral artery of the mouse","volume":"404","author":"Crauwels","year":"2000","journal-title":"Eur. J. Pharmacol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.1161\/STROKEAHA.108.536805","article-title":"Flow-induced dilation is mediated by Akt-dependent activation of endothelial nitric oxide synthase-derived hydrogen peroxide in mouse cerebral arteries","volume":"40","author":"Drouin","year":"2009","journal-title":"Stroke"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e68695","DOI":"10.7554\/eLife.68695","article-title":"Membrane estrogen receptor alpha (ERalpha) participates in flow-mediated dilation in a ligand-independent manner","volume":"10","author":"Favre","year":"2021","journal-title":"eLife"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.niox.2019.07.008","article-title":"Differential effects of resveratrol on the dilator responses of femoral arteries, ex vivo","volume":"92","author":"Diaz","year":"2019","journal-title":"Nitric. Oxide"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e14351","DOI":"10.14814\/phy2.14351","article-title":"Noninvasive sublingual microvascular imaging reveals sex-specific reduction in glycocalyx barrier properties in patients with coronary artery disease","volume":"8","author":"Brands","year":"2020","journal-title":"Physiol. Rep."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1177\/1358863X10361545","article-title":"A pooled analysis of the durability and predictors of treatment response of cilostazol in patients with intermittent claudication","volume":"15","author":"Pande","year":"2010","journal-title":"Vasc. Med."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"328","DOI":"10.1111\/jcpt.13284","article-title":"Cilostazol increases adenosine plasma concentration in patients with acute coronary syndrome","volume":"46","author":"Xue","year":"2021","journal-title":"J. Clin. Pharm. Ther."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1016\/j.brainres.2016.06.036","article-title":"Cilostazol reduces blood brain barrier dysfunction, white matter lesion formation and motor deficits following chronic cerebral hypoperfusion","volume":"1646","author":"Edrissi","year":"2016","journal-title":"Brain Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"H1146","DOI":"10.1152\/ajpheart.00252.2009","article-title":"Intrinsic sex-specific differences in microvascular endothelial cell phosphodiesterases","volume":"298","author":"Wang","year":"2010","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/nri.2016.90","article-title":"Sex differences in immune responses","volume":"16","author":"Klein","year":"2016","journal-title":"Nat. Rev. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Iorga, A., Cunningham, C.M., Moazeni, S., Ruffenach, G., Umar, S., and Eghbali, M. (2017). The protective role of estrogen and estrogen receptors in cardiovascular disease and the controversial use of estrogen therapy. Biol. Sex Differ., 8.","DOI":"10.1186\/s13293-017-0152-8"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ecl.2013.02.003","article-title":"Endogenous sex steroid levels and cardiovascular disease in relation to the menopause: A systematic review","volume":"42","author":"Crandall","year":"2013","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1161\/ATVBAHA.117.310035","article-title":"Sex Chromosome Complement Defines Diffuse Versus Focal Angiotensin II-Induced Aortic Pathology","volume":"38","author":"Alsiraj","year":"2018","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"e000651","DOI":"10.1161\/JAHA.113.000651","article-title":"Gender-specific risk factors for peripheral artery disease in a voluntary screening population","volume":"3","author":"Hiramoto","year":"2014","journal-title":"J. Am. Heart Assoc."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1016\/j.jvs.2012.01.059","article-title":"Sex-based differences in the inflammatory profile of peripheral artery disease and the association with primary patency of lower extremity vein bypass grafts","volume":"56","author":"Hiramoto","year":"2012","journal-title":"J. Vasc. Surg."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3929","DOI":"10.1113\/JP276048","article-title":"Sex differences influencing micro- and macrovascular endothelial phenotype in vitro","volume":"596","author":"Huxley","year":"2018","journal-title":"J. Physiol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1249","DOI":"10.1016\/j.jvs.2014.02.045","article-title":"Gender and racial differences in endothelial oxidative stress and inflammation in patients with symptomatic peripheral artery disease","volume":"61","author":"Gardner","year":"2015","journal-title":"J. Vasc. Surg."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1177\/1358863X15596237","article-title":"Sex-specific predictors of improved walking with step-monitored, home-based exercise in peripheral artery disease","volume":"20","author":"Gardner","year":"2015","journal-title":"Vasc. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"12","DOI":"10.1186\/1475-2840-2-12","article-title":"Platelet-neutrophil conjugate formation is increased in diabetic women with cardiovascular disease","volume":"2","author":"Tuttle","year":"2003","journal-title":"Cardiovasc. Diabetol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"eaax0481","DOI":"10.1126\/scitranslmed.aax0481","article-title":"Platelet regulation of myeloid suppressor of cytokine signaling 3 accelerates atherosclerosis","volume":"11","author":"Barrett","year":"2019","journal-title":"Sci. Transl. Med."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1016\/j.tcm.2015.12.001","article-title":"Tissue factor as a link between inflammation and coagulation","volume":"26","author":"Witkowski","year":"2016","journal-title":"Trends Cardiovasc. Med."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Miceli, G., Basso, M.G., Rizzo, G., Pintus, C., and Tuttolomondo, A. (2022). The Role of the Coagulation System in Peripheral Arterial Disease: Interactions with the Arterial Wall and Its Vascular Microenvironment and Implications for Rational Therapies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232314914"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"e014726","DOI":"10.1161\/JAHA.119.014726","article-title":"Influence of Sex on Platelet Reactivity in Response to Aspirin","volume":"9","author":"Friede","year":"2020","journal-title":"J. Am. Heart Assoc."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/0049-3848(86)90029-0","article-title":"Sex-related differences in the effects of aspirin on the interaction of platelets with subendothelium","volume":"44","author":"Escolar","year":"1986","journal-title":"Thromb. Res."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2342837","DOI":"10.1155\/2020\/2342837","article-title":"Platelet Responses in Cardiovascular Disease: Sex-Related Differences in Nutritional and Pharmacological Interventions","volume":"2020","author":"Gasperi","year":"2020","journal-title":"Cardiovasc. Ther."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"961","DOI":"10.1161\/01.ATV.18.6.961","article-title":"Effect of 17beta-estradiol on inhibition of platelet aggregation in vitro is mediated by an increase in NO synthesis","volume":"18","author":"Nakano","year":"1998","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1053\/ejvs.2002.1795","article-title":"The role of platelets in peripheral vascular disease","volume":"25","author":"Cassar","year":"2003","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1161\/ATVBAHA.120.315033","article-title":"Sex-Specific Platelet Activation Through Protease-Activated Receptors Reverses in Myocardial Infarction","volume":"41","author":"Auerbach","year":"2021","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.expneurol.2014.02.011","article-title":"Sex differences in stroke: The contribution of coagulation","volume":"259","author":"McCullough","year":"2014","journal-title":"Exp. Neurol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1055\/s-0038-1649925","article-title":"Plasma levels of protein S, protein C, and factor X: Effects of sex, hormonal state and age","volume":"74","author":"Henkens","year":"1995","journal-title":"Thromb. Haemost."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1097\/00001721-200011010-00005","article-title":"Plasma fibrinogen, haemostatic factors and prediction of peripheral arterial disease in the Edinburgh Artery Study","volume":"11","author":"Smith","year":"2000","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1055\/s-0037-1615055","article-title":"Sex differences in coagulation and fibrinolysis in subjects with coronary artery disease","volume":"79","author":"Wilson","year":"1998","journal-title":"Thromb. Haemost."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1161\/01.ATV.16.1.160","article-title":"Sex differences in coagulation and fibrinolysis in white subjects with non-insulin-dependent diabetes mellitus","volume":"16","author":"Mansfield","year":"1996","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Ranucci, M., Aloisio, T., Di Dedda, U., Menicanti, L., de Vincentiis, C., Baryshnikova, E., and Surgical and Clinical Outcome REsearch (SCORE) Group (2019). Gender-based differences in platelet function and platelet reactivity to P2Y12 inhibitors. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0225771"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1016\/j.thromres.2018.06.022","article-title":"Gender-related differences in post-discharge bleeding among patients with acute coronary syndrome on dual antiplatelet therapy: A BleeMACS sub-study","volume":"168","author":"Grodecki","year":"2018","journal-title":"Thromb. Res."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Irani, Y.D., Pulford, E., Mortimer, L., Irani, S., Butler, L., Klebe, S., and Williams, K.A. (2019). Sex differences in corneal neovascularization in response to superficial corneal cautery in the rat. PLoS ONE, 14.","DOI":"10.1371\/journal.pone.0221566"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"736303","DOI":"10.3389\/fcvm.2021.736303","article-title":"Angiogenic Secretion Profile of Valvular Interstitial Cells Varies with Cellular Sex and Phenotype","volume":"8","author":"Nelson","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"e21840","DOI":"10.1096\/fj.202001616RR","article-title":"The effects of bone morphogenetic protein 2 and thrombopoietin treatment on angiogenic properties of endothelial cells derived from the lung and bone marrow of young and aged, male and female mice","volume":"35","author":"Dadwal","year":"2021","journal-title":"FASEB J."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"H1287","DOI":"10.1152\/ajpheart.00416.2018","article-title":"Pulmonary endothelial cells exhibit sexual dimorphism in their response to hyperoxia","volume":"315","author":"Zhang","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"587221","DOI":"10.3389\/fphar.2020.587221","article-title":"Sex Differences in the Pro-Angiogenic Response of Human Endothelial Cells: Focus on PFKFB3 and FAK Activation","volume":"11","author":"Boscaro","year":"2020","journal-title":"Front. Pharmacol."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Cattaneo, M.G., Banfi, C., Brioschi, M., Lattuada, D., and Vicentini, L.M. (2021). Sex-dependent differences in the secretome of human endothelial cells. Biol. Sex Differ., 12.","DOI":"10.1186\/s13293-020-00350-3"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"9612","DOI":"10.1038\/s41598-017-10139-x","article-title":"Sex-specific eNOS activity and function in human endothelial cells","volume":"7","author":"Cattaneo","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"e21480","DOI":"10.1096\/fj.202001794RR","article-title":"Estrogen-related receptor alpha is involved in angiogenesis and skeletal muscle revascularization in hindlimb ischemia","volume":"35","author":"Sopariwala","year":"2021","journal-title":"FASEB J."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1022","DOI":"10.1016\/j.jss.2012.04.067","article-title":"Estrogen deficiency attenuates neovascularization in a murine model of hindlimb ischemia","volume":"178","author":"Matsubara","year":"2012","journal-title":"J. Surg. Res."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1042\/cs1040397","article-title":"Vascular endothelial growth factor and tissue factor in patients with established peripheral artery disease: A link between angiogenesis and thrombogenesis?","volume":"104","author":"Makin","year":"2003","journal-title":"Clin. Sci."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1016\/j.ejvs.2009.09.025","article-title":"VEGF: A surrogate marker for peripheral vascular disease","volume":"39","author":"Stehr","year":"2010","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"12367","DOI":"10.1038\/s41598-020-69451-8","article-title":"Intrinsic transcriptomic sex differences in human endothelial cells at birth and in adults are associated with coronary artery disease targets","volume":"10","author":"Hartman","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"1848","DOI":"10.1161\/CIRCULATIONAHA.119.041433","article-title":"Single-Cell RNA Sequencing Unveils Unique Transcriptomic Signatures of Organ-Specific Endothelial Cells","volume":"142","author":"Paik","year":"2020","journal-title":"Circulation"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"590377","DOI":"10.3389\/fgene.2021.590377","article-title":"Single-Cell Transcriptional Profiling Reveals Sex and Age Diversity of Gene Expression in Mouse Endothelial Cells","volume":"12","author":"Huang","year":"2021","journal-title":"Front. Genet."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Zemskova, M., Kurdyukov, S., James, J., McClain, N., Rafikov, R., and Rafikova, O. (2020). Sex-specific stress response and HMGB1 release in pulmonary endothelial cells. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0231267"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.atherosclerosis.2019.10.007","article-title":"Sex-specific metabolic and functional differences in human umbilical vein endothelial cells from twin pairs","volume":"291","author":"Lorenz","year":"2019","journal-title":"Atherosclerosis"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"H897","DOI":"10.1152\/ajpheart.00641.2017","article-title":"Oxygen availability and skeletal muscle oxidative capacity in patients with peripheral artery disease: Implications from in vivo and in vitro assessments","volume":"315","author":"Hart","year":"2018","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1016\/j.jvs.2016.04.041","article-title":"Diminished force production and mitochondrial respiratory deficits are strain-dependent myopathies of subacute limb ischemia","volume":"65","author":"Schmidt","year":"2017","journal-title":"J. Vasc. Surg."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1428","DOI":"10.1161\/CIRCRESAHA.122.322325","article-title":"Transcriptomic and Proteomic of Gastrocnemius Muscle in Peripheral Artery Disease","volume":"132","author":"Ferrucci","year":"2023","journal-title":"Circ. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1210\/edrv.22.1.0417","article-title":"Diabetes and endothelial dysfunction: A clinical perspective","volume":"22","author":"Cipolla","year":"2001","journal-title":"Endocr. Rev."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1056\/NEJM199601183340303","article-title":"Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults","volume":"334","author":"Celermajer","year":"1996","journal-title":"N. Engl. J. Med."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"j5842","DOI":"10.1136\/bmj.j5842","article-title":"Peripheral artery disease","volume":"360","author":"Morley","year":"2018","journal-title":"BMJ (Clin. Res. Ed.)"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"704106","DOI":"10.3389\/fcvm.2021.704106","article-title":"Smoking and the Pathophysiology of Peripheral Artery Disease","volume":"8","author":"Wang","year":"2021","journal-title":"Front. Cardiovasc. Med."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1016\/j.jacc.2019.05.049","article-title":"Cigarette Smoking, Smoking Cessation, and Long-Term Risk of 3 Major Atherosclerotic Diseases","volume":"74","author":"Ding","year":"2019","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Sigvant, B., Lundin, F., Nilsson, B., Bergqvist, D., and Wahlberg, E. (2011). Differences in presentation of symptoms between women and men with intermittent claudication. BMC Cardiovasc. Disord., 11.","DOI":"10.1186\/1471-2261-11-39"},{"key":"ref_95","doi-asserted-by":"crossref","unstructured":"Xu, Y., Harris, K., Pouncey, A.L., Carcel, C., Low, G., Peters, S.A.E., and Woodward, M. (2023). Sex differences in risk factors for incident peripheral artery disease hospitalisation or death: Cohort study of UK Biobank participants. PLoS ONE, 18.","DOI":"10.1371\/journal.pone.0292083"},{"key":"ref_96","doi-asserted-by":"crossref","unstructured":"Pereira-da-Silva, T., Napoleao, P., Costa, M.C., Gabriel, A.F., Selas, M., Silva, F., Enguita, F.J., Ferreira, R.C., and Carmo, M.M. (2021). Cigarette Smoking, miR-27b Downregulation, and Peripheral Artery Disease: Insights into the Mechanisms of Smoking Toxicity. J. Clin. Med., 10.","DOI":"10.3390\/jcm10040890"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"17539447221096940","DOI":"10.1177\/17539447221096940","article-title":"MicroRNAs in peripheral artery disease: Potential biomarkers and pathophysiological mechanisms","volume":"16","author":"Ring","year":"2022","journal-title":"Ther. Adv. Cardiovasc. Dis."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"D\u2019Onofrio, N., Prattichizzo, F., Martino, E., Anastasio, C., Mele, L., La Grotta, R., Sardu, C., Ceriello, A., Marfella, R., and Paolisso, G. (2023). MiR-27b attenuates mitochondrial oxidative stress and inflammation in endothelial cells. Redox. Biol., 62.","DOI":"10.1016\/j.redox.2023.102681"},{"key":"ref_99","first-page":"559","article-title":"Estrogen-regulated miRNA-27b is altered by bisphenol A in human endometrial stromal cells","volume":"156","author":"Reed","year":"2018","journal-title":"Reproduction"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/S0140-6736(13)61249-0","article-title":"Comparison of global estimates of prevalence and risk factors for peripheral artery disease in 2000 and 2010: A systematic review and analysis","volume":"382","author":"Fowkes","year":"2013","journal-title":"Lancet"},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"50","DOI":"10.2337\/dc18-1380","article-title":"Resurgence of Diabetes-Related Nontraumatic Lower-Extremity Amputation in the Young and Middle-Aged Adult U.S. Population","volume":"42","author":"Geiss","year":"2019","journal-title":"Diabetes Care"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/S2213-8587(18)30079-2","article-title":"Sex-specific relevance of diabetes to occlusive vascular and other mortality: A collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies","volume":"6","year":"2018","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Badacz, R., Przewlocki, T., Pieniazek, P., Roslawiecka, A., Kleczynski, P., Legutko, J., Zmudka, K., and Kablak-Ziembicka, A. (2022). MicroRNA-134-5p and the Extent of Arterial Occlusive Disease Are Associated with Risk of Future Adverse Cardiac and Cerebral Events in Diabetic Patients Undergoing Carotid Artery Stenting for Symptomatic Carotid Artery Disease. Molecules, 27.","DOI":"10.3390\/molecules27082472"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1111\/febs.14416","article-title":"MicroRNA-134 inhibits osteosarcoma angiogenesis and proliferation by targeting the VEGFA\/VEGFR1 pathway","volume":"285","author":"Zhang","year":"2018","journal-title":"FEBS J."},{"key":"ref_105","doi-asserted-by":"crossref","unstructured":"Wang, H.W., Su, S.H., Wang, Y.L., Chang, S.T., Liao, K.H., Lo, H.H., Chiu, Y.L., Hsieh, T.H., Huang, T.S., and Lin, C.S. (2016). MicroRNA-134 Contributes to Glucose-Induced Endothelial Cell Dysfunction and This Effect Can Be Reversed by Far-Infrared Irradiation. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0147067"},{"key":"ref_106","first-page":"2090","article-title":"Rivaroxaban in Peripheral Artery Disease after Revascularization. Reply","volume":"383","author":"Bonaca","year":"2020","journal-title":"N. Engl. J. Med."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17439\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T21:38:04Z","timestamp":1760132284000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/24\/24\/17439"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,13]]},"references-count":106,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2023,12]]}},"alternative-id":["ijms242417439"],"URL":"https:\/\/doi.org\/10.3390\/ijms242417439","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,13]]}}}