{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T21:41:43Z","timestamp":1760218903863,"version":"build-2065373602"},"reference-count":33,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2014,2,19]],"date-time":"2014-02-19T00:00:00Z","timestamp":1392768000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The selection of vascular grafts for coronary artery bypass surgery is crucial for a positive outcome. This study aimed to establish a novel line of vascular endothelial cells with a potent anticoagulant effect. A lentiviral vector was used to stably transfect human umbilical vein endothelial cells (HUVECs) with PGI2S alone (HUVEC-PGI2S) or both PGI2S and tPA (HUVEC-PGI2S-tPA). Both HUVEC-PGI2S and HUVEC-PGI2S-tPA cells over-expressing PGI2S and tPA were compared to mock-transfected cells. The enzyme-linked immuno sorbent assay (ELISAs) demonstrated that the anticoagulation components, ATIII and PLG, were up-regulated and coagulation factor FVIII was down-regulated in both cell lines. QRT-PCR and western blotting demonstrated the vasodilation and platelet disaggregation proteins PKA, PKC, and PTGIR were up-regulated in both cell lines, but MAPK expression was not altered in either cell line. However, cell viability and colony formation assays and cell cycle analysis demonstrated that both cell lines had a lower rate of cell growth and induced G1 phase arrest. HUVEC-PGI2S and HUVEC-PGI2S-tPA cells have a potent anticoagulant effect and their use in vascular heterografts may decrease the risk of thrombosis.<\/jats:p>","DOI":"10.3390\/ijms15022826","type":"journal-article","created":{"date-parts":[[2014,2,19]],"date-time":"2014-02-19T11:10:21Z","timestamp":1392808221000},"page":"2826-2839","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Anticoagulant Effect of PGI2S and tPA in Transgenic Umbilical Vein Endothelial Cells Is Linked to Up-Regulation  of PKA and PKC"],"prefix":"10.3390","volume":"15","author":[{"given":"Jian-Hua","family":"Wang","sequence":"first","affiliation":[{"name":"Cardiovascular Surgery Department, Second People\u02bcs Hospital of Guangdong Province,  1 Shi-liu Gang Road, Guangzhou 510317, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin-Jing","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center,  651 Dongfeng Road East, Guangzhou 510060, China"},{"name":"Department of Gynecology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Min","family":"Zhong","sequence":"additional","affiliation":[{"name":"Cardiovascular Surgery Department, Second People\u02bcs Hospital of Guangdong Province,  1 Shi-liu Gang Road, Guangzhou 510317, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhe-Sheng","family":"Wen","sequence":"additional","affiliation":[{"name":"Department of Chest, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East,  Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Ming","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Chest, Second People's Hospital of Guangdong Province, 1 Shi-liu Gang Road, Guangzhou 510317, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong-Xin","family":"Liang","sequence":"additional","affiliation":[{"name":"Cardiovascular Surgery Department, Second People\u02bcs Hospital of Guangdong Province,  1 Shi-liu Gang Road, Guangzhou 510317, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Oncology in Southern China, Sun Yat-sen University Cancer Center,  651 Dongfeng Road East, Guangzhou 510060, China"},{"name":"Department of Gynecology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou 510060, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2014,2,19]]},"reference":[{"key":"ref_1","first-page":"164","article-title":"Cardiology\u2019s 10 greatest discoveries of the 20th century","volume":"29","author":"Mehta","year":"2002","journal-title":"Tex. 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Surg"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1016\/j.molmed.2012.04.013","article-title":"Vascular tissue engineering: The next generation","volume":"18","author":"Cleary","year":"2012","journal-title":"Trends Mol. Med"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1097\/CRD.0b013e3182736190","article-title":"Saphenous vein graft disease: Review of pathophysiology, prevention, and treatment","volume":"21","author":"Kim","year":"2013","journal-title":"Cardiol. Rev"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"679","DOI":"10.1001\/archsurg.1979.01370300033004","article-title":"Seeding endothelium onto canine arterial prostheses: The effects of graft design","volume":"114","author":"Herring","year":"1979","journal-title":"Arch. Surg"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1097\/00000658-197907000-00019","article-title":"Seeding arterial prostheses with vascular endothelium: The nature of the lining","volume":"190","author":"Herring","year":"1979","journal-title":"Ann. Surg"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1097\/MAT.0b013e318031121f","article-title":"An in vitro method for assessing biomaterial-associated platelet activation","volume":"53","author":"LaFayette","year":"2007","journal-title":"ASAIO J"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2547","DOI":"10.1016\/j.biomaterials.2007.01.039","article-title":"The influence of biomaterials on endothelial cell thrombogenicity","volume":"28","author":"McGuigan","year":"2007","journal-title":"Biomaterials"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"575","DOI":"10.1053\/j.jvca.2011.12.004","article-title":"Evaluation of aspirin\u2019s effect on platelet function early after coronary artery bypass grafting","volume":"26","author":"Bednar","year":"2012","journal-title":"J. Cardiothorac. Vasc. Anesth"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1007\/s11626-998-0114-x","article-title":"Modulation of angiotensin-converting enzyme in cultured human vascular endothelial cells","volume":"34","author":"Balyasnikova","year":"1998","journal-title":"In Vitro Cell. Dev. Biol"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1347","DOI":"10.1161\/01.CIR.80.5.1347","article-title":"Seeding of intravascular stents with genetically engineered endothelial cells","volume":"80","author":"Dichek","year":"1989","journal-title":"Circulation"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"6972","DOI":"10.1016\/S0021-9258(19)62711-0","article-title":"The human tissue plasminogen activator gene","volume":"261","author":"Degen","year":"1986","journal-title":"J. Biol. 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Surg"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3846","DOI":"10.4049\/jimmunol.166.6.3846","article-title":"Human vascular endothelial cells stimulate a lower frequency of alloreactive CD8+ pre-CTL and induce less clonal expansion than matching B lymphoblastoid cells: Development of a novel limiting dilution analysis method based on CFSE labeling of lymphocytes","volume":"166","author":"Dengler","year":"2001","journal-title":"J. Immunol"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1504","DOI":"10.1097\/00007890-199312000-00043","article-title":"In vitro induction of endothelial HLA class II antigen expression by cytomegalovirus-activated CD4+ T cells","volume":"56","author":"Waldman","year":"1993","journal-title":"Transplantation"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.1182\/blood.V78.4.1027.1027","article-title":"Recurrent deletion in the human antithrombin III gene","volume":"78","author":"Grundy","year":"1991","journal-title":"Blood"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2159","DOI":"10.1182\/blood.V80.9.2159.2159","article-title":"Molecular basis of inherited human antithrombin deficiency","volume":"80","author":"Blajchman","year":"1992","journal-title":"Blood"},{"key":"ref_25","first-page":"342","article-title":"Natural anticoagulant pathways in normal and transplanted human hearts","volume":"11","author":"Labarrere","year":"1992","journal-title":"J. Heart Lung Transplant"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1186","DOI":"10.1172\/JCI109034","article-title":"Abnormal plasminogen: A hereditary molecular abnormality found in a patient with recurrent thrombosis","volume":"61","author":"Aoki","year":"1978","journal-title":"J. Clin. Invest"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"6104","DOI":"10.1016\/S0021-9258(19)39298-1","article-title":"Characterization of the gene for human plasminogen, a key proenzyme in the fibrinolytic system","volume":"265","author":"Petersen","year":"1990","journal-title":"J. Biol. Chem"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/j.jns.2012.08.020","article-title":"Association between variations in coagulation system genes and carotid plaque","volume":"323","author":"Beecham","year":"2012","journal-title":"J. Neurol. Sci"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1182\/blood-2012-06-435727","article-title":"Cellular and molecular basis of von Willebrand disease: Studies on blood outgrowth endothelial cells","volume":"121","author":"Starke","year":"2013","journal-title":"Blood"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1042\/bj3530503","article-title":"Vascular endothelial growth factor-induced prostacyclin production is mediated by a protein kinase C (PKC)-dependent activation of extracellular signal-regulated protein kinases 1 and 2 involving PKC-\u03b4 and by mobilization of intracellular Ca2+","volume":"353","author":"Gliki","year":"2001","journal-title":"Biochem. 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