{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:34:15Z","timestamp":1760236455318,"version":"build-2065373602"},"reference-count":47,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,11,23]],"date-time":"2021-11-23T00:00:00Z","timestamp":1637625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Research of the State of North Rhine-Westphalia","award":["START-13\/17"],"award-info":[{"award-number":["START-13\/17"]}]},{"DOI":"10.13039\/501100001711","name":"Schweizerischer Nationalfonds zur F\u00f6rderung der Wissenschaftlichen Forschung","doi-asserted-by":"publisher","award":["108 258","122 504"],"award-info":[{"award-number":["108 258","122 504"]}],"id":[{"id":"10.13039\/501100001711","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Liver cirrhosis has been associated with an increased risk of coronary artery disease and clinical complications following percutaneous coronary revascularization. The present study is based on the hypothesis that cirrhosis may influence intimal hyperplasia following PCI. Sera from 10 patients with alcoholic liver cirrhosis and 10 age-matched healthy controls were used to stimulate cultured human coronary artery smooth muscle cells (HCASMC) for 48 h. HCASMC proliferation, migration, gene expression and apoptosis were investigated. Serum concentrations of growth factors and markers of liver function were also determined in patients and healthy controls. Treatment of HCASMC with patient sera reduced cell proliferation and migration (p &lt; 0.05 vs. healthy controls), whereas apoptosis was unaffected (p = 0.160). Expression of genes associated with a synthetic vascular smooth muscle cell phenotype was decreased in cells stimulated with serum from cirrhotic patients (RBP1, p = 0.001; SPP1, p = 0.003; KLF4, p = 0.004). Platelet-derived growth factor-BB serum concentrations were lower in patients (p = 0.001 vs. controls). The results suggest the presence of circulating factors in patients with alcoholic liver cirrhosis affecting coronary smooth muscle cell growth. These findings may have implications for clinical outcomes following percutaneous coronary revascularization in these patients.<\/jats:p>","DOI":"10.3390\/jcm10235471","type":"journal-article","created":{"date-parts":[[2021,12,1]],"date-time":"2021-12-01T01:43:22Z","timestamp":1638323002000},"page":"5471","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Serum from Patients with Severe Alcoholic Liver Cirrhosis Inhibits Proliferation and Migration of Human Coronary Artery Smooth Muscle Cells"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8928-338X","authenticated-orcid":false,"given":"Mare","family":"Mechelinck","sequence":"first","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Miriam","family":"Peschel","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1445-608X","authenticated-orcid":false,"given":"Moriz A.","family":"Habigt","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniela","family":"Kroy","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine III, Gastroenterology, Metabolic Diseases and Intensive Care, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Lehrke","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine I, Cardiology, Angiology and Internal Intensive Care Medicine, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius J.","family":"Helmedag","sequence":"additional","affiliation":[{"name":"Department of General, Visceral and Transplantation Surgery, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rolf","family":"Rossaint","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthias","family":"Barton","sequence":"additional","affiliation":[{"name":"Molecular Internal Medicine, University of Z\u00fcrich, 8057 Z\u00fcrich, Switzerland"},{"name":"Andreas Gr\u00fcntzig Foundation, 8001 Z\u00fcrich, Switzerland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9436-7353","authenticated-orcid":false,"given":"Marc","family":"Hein","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Faculty of Medicine, RWTH Aachen University, 52074 Aachen, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"209","DOI":"10.2174\/1570161115666170622074007","article-title":"NAFLD-NASH: An under-recognized epidemic","volume":"16","author":"Jennings","year":"2018","journal-title":"Curr. Vasc. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1097\/00007890-199503270-00010","article-title":"The prevalence of coronary artery disease in liver transplant candidates over age 50","volume":"59","author":"Carey","year":"1995","journal-title":"Transplantation"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1053\/jlts.2001.26063","article-title":"Detection and treatment of coronary artery disease in liver transplant candidates","volume":"7","author":"Keeffe","year":"2001","journal-title":"Liver Transpl."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1002\/lt.22035","article-title":"Coronary artery disease in orthotopic liver transplantation: Pretransplant assessment and management","volume":"16","author":"Ehtisham","year":"2010","journal-title":"Liver Transpl."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1093\/eurheartj\/ehw106","article-title":"2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of 10 societies and by invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR)","volume":"37","author":"Piepoli","year":"2016","journal-title":"Eur. Heart J."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1093\/eurheartj\/ehz425","article-title":"2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes","volume":"41","author":"Knuuti","year":"2020","journal-title":"Eur. Heart J."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1016\/j.jacc.2014.07.012","article-title":"AHA\/ACC\/HHS strategies to enhance application of clinical practice guidelines in patients with cardiovascular disease and comorbid conditions: From the American Heart Association, American College of Cardiology, and U.S. Department of Health and Human Services","volume":"64","author":"Arnett","year":"2014","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e44","DOI":"10.1016\/j.jacc.2012.07.013","article-title":"2012 ACCF\/AHA\/ACP\/AATS\/PCNA\/SCAI\/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease: A report of the American College of Cardiology Foundation\/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons","volume":"60","author":"Fihn","year":"2012","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1385","DOI":"10.1016\/j.jhep.2014.08.010","article-title":"Cirrhosis-associated immune dysfunction: Distinctive features and clinical relevance","volume":"61","author":"Albillos","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1111\/j.1478-3231.2009.02058.x","article-title":"Morbidity and mortality following coronary artery bypass graft surgery in patients with cirrhosis: A population-based study","volume":"29","author":"Shaheen","year":"2009","journal-title":"Liver Int"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1016\/j.athoracsur.2011.01.022","article-title":"Coronary revascularization in patients with liver cirrhosis","volume":"91","author":"Marui","year":"2011","journal-title":"Ann. Thorac. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.amjcard.2020.01.052","article-title":"Impact of cirrhosis on 90-day outcomes after percutaneous coronary intervention (from A Nationwide Database)","volume":"125","author":"Lu","year":"2020","journal-title":"Am. J. Cardiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"16016","DOI":"10.1038\/ncomms16016","article-title":"SRSF1 promotes vascular smooth muscle cell proliferation through a Delta133p53\/EGR1\/KLF5 pathway","volume":"8","author":"Xie","year":"2017","journal-title":"Nat. Commun."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"104","DOI":"10.1161\/CIRCINTERVENTIONS.110.957332","article-title":"Vascular smooth muscle cell proliferation in restenosis","volume":"4","author":"Marx","year":"2011","journal-title":"Circ. Cardiovasc. Interv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1093\/cvr\/cvt115","article-title":"Biological responses in stented arteries","volume":"99","author":"Chaabane","year":"2013","journal-title":"Cardiovasc. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.jhep.2008.05.024","article-title":"Clinical and pathologic risk factors for atherosclerosis in cirrhosis: A comparison between NASH-related cirrhosis and cirrhosis due to other aetiologies","volume":"49","author":"Kadayifci","year":"2008","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.jhep.2009.06.012","article-title":"Coronary artery disease in liver cirrhosis: Does the aetiology of liver disease matter?","volume":"51","author":"Kalaitzakis","year":"2009","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.jclinane.2013.06.001","article-title":"Coronary artery disease and its risk factors in patients presenting for liver transplantation","volume":"25","author":"Gologorsky","year":"2013","journal-title":"J. Clin. Anesth."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/j.amjcard.2011.07.013","article-title":"Comparison of the frequency of coronary artery disease in alcohol-related versus non-alcohol-related endstage liver disease","volume":"108","author":"Patel","year":"2011","journal-title":"Am. J. Cardiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1161\/CIRCULATIONAHA.114.009278","article-title":"Prevalence and prediction of coronary artery disease in patients with liver cirrhosis: A registry-based matched case-control study","volume":"130","author":"An","year":"2014","journal-title":"Circulation"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.vph.2004.10.002","article-title":"Differential effects of rapamycin, cyclosporine A, and FK506 on human coronary artery smooth muscle cell proliferation and signalling","volume":"41","author":"Hafizi","year":"2004","journal-title":"Vasc. Pharmacol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1021\/pr800545q","article-title":"Standard operating procedures for serum and plasma collection: Early detection research network consensus statement standard operating procedure integration working group","volume":"8","author":"Tuck","year":"2009","journal-title":"J. Proteome Res."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7928","DOI":"10.4049\/jimmunol.0804112","article-title":"Atherogenic lipids induce high-density lipoprotein uptake and cholesterol efflux in human macrophages by up-regulating transmembrane chemokine CXCL16 without engaging CXCL16-dependent cell adhesion","volume":"182","author":"Barlic","year":"2009","journal-title":"J. Immunol."},{"key":"ref_24","first-page":"287","article-title":"Smooth muscle homeostasis in human atherosclerotic plaques through interleukin 15 signalling","volume":"4","author":"Teeling","year":"2011","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1186\/1476-511X-9-61","article-title":"Cholesterol in human atherosclerotic plaque is a marker for underlying disease state and plaque vulnerability","volume":"9","author":"Chen","year":"2010","journal-title":"Lipids Health Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2780","DOI":"10.1111\/jcmm.12661","article-title":"The IkappaB kinase inhibitor ACHP strongly attenuates TGFbeta1-induced myofibroblast formation and collagen synthesis","volume":"19","author":"Mia","year":"2015","journal-title":"J. Cell Mol. Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/S0006-291X(03)00068-8","article-title":"Heparin inhibits SMC growth in the presence of human and fetal bovine serum","volume":"302","author":"Cindhuchao","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e1251","DOI":"10.1038\/cddis.2014.229","article-title":"Sulfur dioxide inhibits vascular smooth muscle cell proliferation via suppressing the Erk\/MAP kinase pathway mediated by cAMP\/PKA signaling","volume":"5","author":"Liu","year":"2014","journal-title":"Cell Death Dis."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1093\/cvr\/cvw258","article-title":"Tipifarnib prevents development of hypoxia-induced pulmonary hypertension","volume":"113","author":"Duluc","year":"2017","journal-title":"Cardiovasc. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nprot.2007.30","article-title":"In vitro scratch assay: A convenient and inexpensive method for analysis of cell migration in vitro","volume":"2","author":"Liang","year":"2007","journal-title":"Nat. Protoc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/j.atherosclerosis.2020.09.007","article-title":"Long noncoding RNA ZNF800 suppresses proliferation and migration of vascular smooth muscle cells by upregulating PTEN and inhibiting AKT\/mTOR\/HIF-1alpha signaling","volume":"312","author":"Lu","year":"2020","journal-title":"Atherosclerosis"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"204","DOI":"10.5551\/jat.19448","article-title":"Oxidized high-density lipoprotein induces the proliferation and migration of vascular smooth muscle cells by promoting the production of ROS","volume":"21","author":"Wang","year":"2014","journal-title":"J. Atheroscler Thromb."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Fenu, M., Bettermann, T., Vogl, C., Darwish-Miranda, N., Schramel, J., Jenner, F., and Ribitsch, I. (2019). A novel magnet-based scratch method for standardisation of wound-healing assays. Sci. Rep., 9.","DOI":"10.1038\/s41598-019-48930-7"},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Martelli, F., Rangrez, A.Y., M\u2019Baya-Moutoula, E., Metzinger-Le Meuth, V., H\u00e9naut, L., Djelouat, M.S.e.I., Benchitrit, J., Massy, Z.A., and Metzinger, L. (2012). Inorganic phosphate accelerates the migration of vascular smooth muscle cells: Evidence for the involvement of miR-223. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0047807"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1007\/s00109-006-0097-6","article-title":"Quantitative real-time RT-PCR data analysis: Current concepts and the novel \"gene expression\u2019s CT difference\" formula","volume":"84","author":"Schefe","year":"2006","journal-title":"J. Mol. Med."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1510","DOI":"10.1161\/01.ATV.0000090130.85752.ED","article-title":"Arterial smooth muscle cell heterogeneity: Implications for atherosclerosis and restenosis development","volume":"23","author":"Hao","year":"2003","journal-title":"Arterioscler Thromb. Vasc. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"692","DOI":"10.1161\/CIRCRESAHA.115.306361","article-title":"Vascular smooth muscle cells in atherosclerosis","volume":"118","author":"Bennett","year":"2016","journal-title":"Circ. Res."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"9719","DOI":"10.1074\/jbc.M412862200","article-title":"Kruppel-like factor 4 abrogates myocardin-induced activation of smooth muscle gene expression","volume":"280","author":"Liu","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"8361","DOI":"10.1074\/jbc.M111.286203","article-title":"A novel RhoA\/ROCK-CPI-17-MEF2C signaling pathway regulates vascular smooth muscle cell gene expression","volume":"287","author":"Pagiatakis","year":"2012","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.1161\/hq0701.092144","article-title":"Phenotypic heterogeneity influences apoptotic susceptibility to retinoic acid and cis-platinum of rat arterial smooth muscle cells in vitro: Implications for the evolution of experimental intimal thickening","volume":"21","author":"Orlandi","year":"2001","journal-title":"Arterioscler Thromb. Vasc. Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.jhep.2014.05.047","article-title":"Vascular pathobiology in chronic liver disease and cirrhosis\u2014current status and future directions","volume":"61","author":"Iwakiri","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19948","DOI":"10.1074\/jbc.M709428200","article-title":"Proliferation versus migration in platelet-derived growth factor signaling: The key role of endocytosis","volume":"283","author":"Comito","year":"2008","journal-title":"J. Biol. Chem."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Ravindran, D., Cartland, S.P., Bursill, C.A., and Kavurma, M.M. (2019). Broad-spectrum chemokine inhibition blocks inflammation-induced angiogenesis, but preserves ischemia-driven angiogenesis. FASEB J., fj201900232RR.","DOI":"10.1096\/fj.201900232RR"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1097\/MEG.0b013e328351db6e","article-title":"High-sensitivity C-reactive protein levels predict survival and are related to haemodynamics in alcoholic cirrhosis","volume":"24","author":"Mortensen","year":"2012","journal-title":"Eur. J. Gastroenterol. Hepatol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1161\/hc0102.101369","article-title":"Adenovirus-mediated heme oxygenase-1 gene expression stimulates apoptosis in vascular smooth muscle cells","volume":"105","author":"Liu","year":"2002","journal-title":"Circulation"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1030","DOI":"10.1161\/CIRCULATIONAHA.104.528802","article-title":"Bilirubin: A natural inhibitor of vascular smooth muscle cell proliferation","volume":"112","author":"Ollinger","year":"2005","journal-title":"Circulation"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1111\/j.1600-6143.2012.04293.x","article-title":"Liver transplantation outcome in patients with angiographically proven coronary artery disease: A multi-institutional study","volume":"13","author":"Wray","year":"2013","journal-title":"Am. J. Transpl."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/23\/5471\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:34:34Z","timestamp":1760168074000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/23\/5471"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,23]]},"references-count":47,"journal-issue":{"issue":"23","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["jcm10235471"],"URL":"https:\/\/doi.org\/10.3390\/jcm10235471","relation":{},"ISSN":["2077-0383"],"issn-type":[{"type":"electronic","value":"2077-0383"}],"subject":[],"published":{"date-parts":[[2021,11,23]]}}}