{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T21:56:41Z","timestamp":1791323801134,"version":"4.3.1"},"reference-count":21,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"3","license":[{"start":{"date-parts":[[2015,9,1]],"date-time":"2015-09-01T00:00:00Z","timestamp":1441065600000},"content-version":"tdm","delay-in-days":2556,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2008,9]]},"abstract":"<jats:sec>\n            <jats:title>Abstract<\/jats:title>\n            <jats:p>\n                                 <jats:bold>Capillarization precedes hepatic fibrosis. We hypothesize that capillarization of sinusoidal endothelial cells (SEC) is permissive for hepatic stellate cell (HSC) activation and therefore permissive for fibrosis. We examined whether freshly isolated SECs prevent activation of HSCs and promote reversion to quiescence, and whether this effect was lost in capillarization. HSCs were cultured alone or co-cultured with differentiated or capillarized SECs. Results: Co-culture with freshly isolated SECs markedly decreased HSC activation after 3 days in culture, but co-culture with capillarized SEC had no effect. Inhibition of nitric oxide (NO) synthesis abolished SEC suppression of HSC activation. Activated HSCs reverted to quiescence when co-cultured with SEC plus vascular endothelial growth factor (VEGF) (that is, with SECs that maintained differentiation), but co-culture with capillarized SECs did not. Reversion of activated HSCs to quiescence in the presence of SECs plus VEGF was abolished by inhibition of NO synthesis. To establish whether there was indeed reversion, activated and quiescent HSCs were counted before and 3 days after adding freshly isolated SECs plus VEGF to activated HSCs, and proliferation was quantified in quiescent HSCs; the stoichiometry demonstrated reversion.<\/jats:bold>\n                                 <jats:bold>\n                                    Conclusion:\n                                 <\/jats:bold>\n                                 <jats:bold>Differentiated SECs prevent HSC activation and promote reversion of activated HSCs to quiescence through VEGF-stimulated NO production. Capillarized SECs do not promote HSC quiescence, because of loss of VEGF-stimulated NO production. (Hepatology 2008.)<\/jats:bold>\n                              <\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.22351","type":"journal-article","created":{"date-parts":[[2008,4,11]],"date-time":"2008-04-11T19:17:00Z","timestamp":1207941420000},"page":"920-930","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":378,"title":["Sinusoidal endothelial cells prevent rat stellate cell activation and promote reversion to quiescence"],"prefix":"10.1097","volume":"48","author":[{"given":"Laurie D.","family":"DeLeve","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangdong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yumei","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"R1-25-20241202","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/S0016-5085(63)80130-4","article-title":"Capillarization of hepatic sinusoids in man.","volume":"44","author":"Schaffner","year":"1963","journal-title":"Gastroenterology"},{"key":"R2-25-20241202","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1002\/hep.1840070117","article-title":"Alcoholic liver injury: defenestration in noncirrhotic liversa scanning electron microscopic study.","volume":"7","author":"Horn","year":"1987","journal-title":"HEPATOLOGY"},{"key":"R3-25-20241202","doi-asserted-by":"crossref","first-page":"891","DOI":"10.1002\/hep.1840170520","article-title":"Defenestration of the Sinusoidal Endothelial Cell in a Rat Model of Cirrhosis.","volume":"17","author":"Mori","year":"1993","journal-title":"HEPATOLOGY"},{"key":"R4-25-20241202","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1111\/j.1600-0676.1985.tb00253.x","article-title":"Early alcoholic liver injury: changes of the Disse space in acinar zone 3.","volume":"5","author":"Horn","year":"1985","journal-title":"Liver"},{"issue":"Suppl 1","key":"R5-25-20241202","first-page":"67","article-title":"Experimental study of the reversibility of sinusoidal capillarization.","volume":"29","author":"Mori","year":"1994","journal-title":"Alcohol and Alcoholism"},{"key":"R6-25-20241202","doi-asserted-by":"crossref","first-page":"512","DOI":"10.1161\/01.RES.0000182903.16652.d7","article-title":"Endothelialpericyte interactions.","volume":"97","author":"Armulik","year":"2005","journal-title":"Circulation Res"},{"key":"R7-25-20241202","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.jvs.2004.12.024","article-title":"Endothelial cell activation of the smooth muscle cell phosphoinositide 3kinaseAkt pathway promotes differentiation.","volume":"41","author":"Brown","year":"2005","journal-title":"J Vasc Surg"},{"key":"R8-25-20241202","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.jvs.2004.11.016","article-title":"Shear stressstimulated endothelial cells induce smooth muscle cell chemotaxis via plateletderived growth factorBB and interleukin1alpha.","volume":"41","author":"Dardik","year":"2005","journal-title":"J Vasc Surg"},{"key":"R9-25-20241202","doi-asserted-by":"crossref","first-page":"G757","DOI":"10.1152\/ajpgi.00017.2004","article-title":"Rat liver sinusoidal endothelial cell phenotype is under paracrine and autocrine control.","volume":"287","author":"DeLeve","year":"2004","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R10-25-20241202","doi-asserted-by":"crossref","first-page":"G1187","DOI":"10.1152\/ajpgi.00229.2006","article-title":"Rat liver endothelial cells isolated by antiCD31 immunomagnetic sorting lack fenestrae and sieve plates.","volume":"291","author":"DeLeve","year":"2006","journal-title":"Am J Physiol Gastrointest Liver Physiol"},{"key":"R11-25-20241202","doi-asserted-by":"crossref","first-page":"814","DOI":"10.1002\/hep.1840060503","article-title":"Ethanolinduced liver fibrosis in rats fed high fat diet.","volume":"6","author":"Tsukamoto","year":"1986","journal-title":"HEPATOLOGY"},{"key":"R12-25-20241202","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/0003-2697(82)90118-X","article-title":"Analysis of nitrate, nitrite, and 15Nnitrate in biological fluids.","volume":"126","author":"Green","year":"1982","journal-title":"Anal Biochem"},{"key":"R13-25-20241202","doi-asserted-by":"crossref","first-page":"900","DOI":"10.1002\/hep.1840380416","article-title":"Decreased hepatic nitric oxide production contributes to the development of rat sinusoidal obstruction syndrome.","volume":"38","author":"DeLeve","year":"2003","journal-title":"HEPATOLOGY"},{"key":"R15-25-20241202","first-page":"266A","article-title":"Capillarization is due to the loss of paracrine and autocrine control of the sinusoidal endothelial cell (SEC) phenotype. 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