{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,5]],"date-time":"2026-09-05T04:31:51Z","timestamp":1788582711566,"version":"build-2803163510"},"reference-count":47,"publisher":"Aging and Disease","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Aging and disease"],"published-print":{"date-parts":[[2019]]},"DOI":"10.14336\/ad.2019.0127","type":"journal-article","created":{"date-parts":[[2019,8,1]],"date-time":"2019-08-01T21:04:16Z","timestamp":1564693456000},"page":"684","source":"Crossref","is-referenced-by-count":61,"title":["Aging Influences Hepatic Microvascular Biology and Liver Fibrosis in Advanced Chronic Liver Disease"],"prefix":"10.14336","volume":"10","author":[{"given":"Raquel","family":"Maeso-D\u00edaz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mart\u00ed","family":"Ortega-Ribera","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica","family":"Lafoz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Jos\u00e9","family":"Lozano","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Baiges","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rub\u00e9n","family":"Franc\u00e9s","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agust\u00edn","family":"Albillos","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Peralta","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Carlos","family":"Garc\u00eda-Pag\u00e1n","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Bosch","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria C","family":"Cogger","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordi","family":"Gracia-Sancho","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"5462","reference":[{"key":"key-10.14336\/AD.2019.0127-1","unstructured":"He W, Goodkind D, Kowal P (2016). An Aging World: 2015 International Population Reports. US Gov Publ Off Washington, DC P95\/16-1."},{"key":"key-10.14336\/AD.2019.0127-2","doi-asserted-by":"crossref","unstructured":"Le Couteur DG, McLean AJ (1998). The aging liver: Drug clearance and an oxygen diffusion barrier hypothesis. Clin Pharmacokinet, 34: 359-373.","DOI":"10.2165\/00003088-199834050-00003"},{"key":"key-10.14336\/AD.2019.0127-3","doi-asserted-by":"crossref","unstructured":"Maeso-D\u00edaz R, Ortega-Ribera M, Fern\u00e1ndez-Iglesias A, Hide D, Mu\u00f1oz L, Hessheimer AJ, et al. (2018). Effects of aging on liver microcirculatory function and sinusoidal phenotype. Aging Cell, 17: e12829.","DOI":"10.1111\/acel.12829"},{"key":"key-10.14336\/AD.2019.0127-4","doi-asserted-by":"crossref","unstructured":"Blachier M, Leleu H, Peck-Radosavljevic M, Valla DC, Roudot-Thoraval F (2013). The burden of liver disease in Europe: A review of available epidemiological data. J Hepatol, 58: 593-608.","DOI":"10.1016\/j.jhep.2012.12.005"},{"key":"key-10.14336\/AD.2019.0127-5","doi-asserted-by":"crossref","unstructured":"Marcellin P, Kutala BK (2018). Liver diseases: A major, neglected global public health problem requiring urgent actions and large-scale screening. Liver Int, 38: 2-6.","DOI":"10.1111\/liv.13682"},{"key":"key-10.14336\/AD.2019.0127-6","doi-asserted-by":"crossref","unstructured":"Angulo P, Keach JC, Batts KP, Lindor KD (1999). Independent predictors of liver fibrosis in patients with nonalcoholic steatohepatitis. Hepatology, 30: 1356-1362.","DOI":"10.1002\/hep.510300604"},{"key":"key-10.14336\/AD.2019.0127-7","doi-asserted-by":"crossref","unstructured":"Tsochatzis EA, Bosch J, Burroughs AK (2014). Liver cirrhosis. Lancet, 383: 1749-1761.","DOI":"10.1016\/S0140-6736(14)60121-5"},{"key":"key-10.14336\/AD.2019.0127-8","doi-asserted-by":"crossref","unstructured":"Sheedfar F, Biase S Di, Koonen D, Vinciguerra M (2013). Liver diseases and aging: Friends or foes? Aging Cell, 12: 950-954.","DOI":"10.1111\/acel.12128"},{"key":"key-10.14336\/AD.2019.0127-9","doi-asserted-by":"crossref","unstructured":"Ramirez T, Li YM, Yin S, Xu MJ, Feng D, Zhou Z, et al. (2017). Aging aggravates alcoholic liver injury and fibrosis in mice by downregulating sirtuin 1 expression. J Hepatol, 66: 601-609.","DOI":"10.1016\/j.jhep.2016.11.004"},{"key":"key-10.14336\/AD.2019.0127-10","doi-asserted-by":"crossref","unstructured":"Collins BH, Holzknecht ZE, Lynn KA, Sempowski GD, Smith CC, Liu S, et al. (2013). Association of age-dependent liver injury and fibrosis with immune cell populations. Liver Int, 33: 1175-1186.","DOI":"10.1111\/liv.12202"},{"key":"key-10.14336\/AD.2019.0127-11","doi-asserted-by":"crossref","unstructured":"Kim IH, Xu J, Liu X, Koyama Y, Ma HY, Diggle K, et al. (2016). Aging increases the susceptibility of hepatic inflammation, liver fibrosis and aging in response to high-fat diet in mice. Age (Omaha), 38: 291-302.","DOI":"10.1007\/s11357-016-9938-6"},{"key":"key-10.14336\/AD.2019.0127-12","doi-asserted-by":"crossref","unstructured":"Trebicka J, Hennenberg M, Laleman W, Shelest N, Biecker E, Schepke M, et al. (2007). Atorvastatin lowers portal pressure in cirrhotic rats by inhibition of RhoA\/Rho-kinase and activation of endothelial nitric oxide synthase. Hepatology, 46: 242-253.","DOI":"10.1002\/hep.21673"},{"key":"key-10.14336\/AD.2019.0127-13","doi-asserted-by":"crossref","unstructured":"Abraldes JG, Rodr\u00edguez-Vilarrupla A, Graupera M, Zafra C, Garc\u00eda-Calder\u00f3 H, Garc\u00eda-Pag\u00e1n JC, et al. (2007). Simvastatin treatment improves liver sinusoidal endothelial dysfunction in CCl4cirrhotic rats. J Hepatol, 46: 1040-1046.","DOI":"10.1016\/j.jhep.2007.01.020"},{"key":"key-10.14336\/AD.2019.0127-14","doi-asserted-by":"crossref","unstructured":"Marrone G, Maeso-D\u00edaz R, Garc\u00eda-Cardena G, Abraldes JG, Garc\u00eda-Pag\u00e1n JC, Bosch J, et al. (2015). KLF2 exerts antifibrotic and vasoprotective effects in cirrhotic rat livers: Behind the molecular mechanisms of statins. Gut, 64: 1434-1443.","DOI":"10.1136\/gutjnl-2014-308338"},{"key":"key-10.14336\/AD.2019.0127-15","doi-asserted-by":"crossref","unstructured":"Meireles CZ, Pasarin M, Lozano JJ, Garc\u00eda-Calder\u00f3 H, Gracia-Sancho J, Garc\u00eda-Pag\u00e1n JC, et al. (2017). Simvastatin attenuates liver injury in rodents with biliary cirrhosis submitted to hemorrhage\/resuscitation. Shock, 47: 370-377.","DOI":"10.1097\/SHK.0000000000000734"},{"key":"key-10.14336\/AD.2019.0127-16","doi-asserted-by":"crossref","unstructured":"Tripathi DM, Vilaseca M, Lafoz E, Garcia-Caldero H, Haute GV, Fern\u00e1ndez-Iglesias A, et al. (2018). Simvastatin Prevents Progression of Acute on Chronic Liver Failure in Rats With Cirrhosis and Portal Hypertension. Gastroenterology, 155: 1564-1577.","DOI":"10.1053\/j.gastro.2018.07.022"},{"key":"key-10.14336\/AD.2019.0127-17","unstructured":"Abraldes JG, Villanueva C, Aracil C, Turnes J, Hernandez-Guerra M, Genesca J, et al. (2016). Addition of Simvastatin to Standard Therapy for the Prevention of Variceal Rebleeding Does Not Reduce Rebleeding but Increases Survival in Patients with Cirrhosis. Gastroenterology, 150: 1160-1170."},{"key":"key-10.14336\/AD.2019.0127-18","doi-asserted-by":"crossref","unstructured":"Bosch J, Abraldes JG, Fern\u00e1ndez M, Garc\u00eda-Pag\u00e1n JC (2010). Hepatic endothelial dysfunction and abnormal angiogenesis: New targets in the treatment of portal hypertension. J Hepatol, 53: 558-567.","DOI":"10.1016\/j.jhep.2010.03.021"},{"key":"key-10.14336\/AD.2019.0127-19","doi-asserted-by":"crossref","unstructured":"Mohanty A, Tate JP, Garcia-Tsao G (2016). Statins Are Associated with a Decreased Risk of Decompensation and Death in Veterans with Hepatitis C-Related Compensated Cirrhosis. Gastroenterology, 150: 430-440.","DOI":"10.1053\/j.gastro.2015.10.007"},{"key":"key-10.14336\/AD.2019.0127-20","doi-asserted-by":"crossref","unstructured":"Gracia-Sancho J, Lavi\u00f1a B, Rodr\u00edguez-Vilarrupla A, Brandes RP, Fern\u00e1ndez M, Bosch J, et al. (2007). Evidence Against a Role for NADPH Oxidase Modulating Hepatic Vascular Tone in Cirrhosis. Gastroenterology, 133: 959-966.","DOI":"10.1053\/j.gastro.2007.06.021"},{"key":"key-10.14336\/AD.2019.0127-21","doi-asserted-by":"crossref","unstructured":"Russo L, Gracia-Sancho J, Garc\u00eda-Calder\u00f3 H, Marrone G, Garc\u00eda-Pag\u00e1n JC, et al. (2012). Addition of simvastatin to cold storage solution prevents endothelial dysfunction in explanted rat livers. Hepatology, 55: 921-930.","DOI":"10.1002\/hep.24755"},{"key":"key-10.14336\/AD.2019.0127-22","doi-asserted-by":"crossref","unstructured":"De Mesquita FC, Guix\u00e9-Muntet S, Fern\u00e1ndez-Iglesias A, Maeso-D\u00edaz R, Vila S, Hide D, et al. (2017). Liraglutide improves liver microvascular dysfunction in cirrhosis: Evidence from translational studies. Sci Rep, 7: 1-10.","DOI":"10.1038\/s41598-017-02866-y"},{"key":"key-10.14336\/AD.2019.0127-23","doi-asserted-by":"crossref","unstructured":"Le Couteur DG, Cogger VC, Markus AMA, Harvey PJ, Yin ZL, Ansselin AD, et al. (2001). Pseudocapillarization and associated energy limitation in the aged rat liver. Hepatology, 33: 537-543.","DOI":"10.1053\/jhep.2001.22754"},{"key":"key-10.14336\/AD.2019.0127-24","doi-asserted-by":"crossref","unstructured":"Gracia-Sancho J, Lavi\u00f1a B, Rodr\u00edguez-Vilarrupla A, Garc\u00eda-Calder\u00f3 H, Fern\u00e1ndez M, et al. (2008). Increased oxidative stress in cirrhotic rat livers: A potential mechanism contributing to reduced nitric oxide bioavailability. Hepatology, 47: 1248-1256.","DOI":"10.1002\/hep.22166"},{"key":"key-10.14336\/AD.2019.0127-25","doi-asserted-by":"crossref","unstructured":"Hide D, Ortega-Ribera M, Fern\u00e1ndez-Iglesias A, Fondevila C, Salvad\u00f3 MJ, Arola L, et al. (2014). A novel form of the human manganese superoxide dismutase protects rat and human livers undergoing ischaemia and reperfusion injury. Clin Sci, 127: 527-537.","DOI":"10.1042\/CS20140125"},{"key":"key-10.14336\/AD.2019.0127-26","doi-asserted-by":"crossref","unstructured":"Vilaseca M, Garc\u00eda-Calder\u00f3 H, Lafoz E, Ruart M, L\u00f3pez-Sanjurjo C, Murphy MP, et al. (2017). Mitochondria-targeted antioxidant mitoquinone deactivates human and rat hepatic stellate cells and reduces portal hypertension in cirrhotic rats. Liver Int, 37: 1002-1012.","DOI":"10.1111\/liv.13436"},{"key":"key-10.14336\/AD.2019.0127-27","doi-asserted-by":"crossref","unstructured":"Du P, Kibbe WA, Lin SM (2008). lumi: A pipeline for processing Illumina microarray. Bioinformatics, 24: 1547-1548.","DOI":"10.1093\/bioinformatics\/btn224"},{"key":"key-10.14336\/AD.2019.0127-28","doi-asserted-by":"crossref","unstructured":"Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W, et al. (2015). limma powers di erential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res, 43: e47.","DOI":"10.1093\/nar\/gkv007"},{"key":"key-10.14336\/AD.2019.0127-29","doi-asserted-by":"crossref","unstructured":"Liberzon A, Subramanian A, Pinchback R, Thorvaldsd\u00f3ttir H, Tamayo P, Mesirov JP (2011). Molecular signatures database (MSigDB) 3.0. Bioinformatics, 27: 1739-1740.","DOI":"10.1093\/bioinformatics\/btr260"},{"key":"key-10.14336\/AD.2019.0127-30","doi-asserted-by":"crossref","unstructured":"Yamazaki H, Oda M, Takahashi Y, Iguchi H, Yoshimura K, Okada N, et al. (2013). Relation between Ultrastructural Localization, Changes in Caveolin-1, and Capillarization of Liver Sinusoidal Endothelial Cells in Human Hepatitis C-Related Cirrhotic Liver. J Histochem Cytochem, 61: 169-176.","DOI":"10.1369\/0022155412468590"},{"key":"key-10.14336\/AD.2019.0127-31","doi-asserted-by":"crossref","unstructured":"Frith J, Jones D, Newton JL (2009). Chronic liver disease in an ageing population. Age Ageing, 38: 11-18.","DOI":"10.1093\/ageing\/afn242"},{"key":"key-10.14336\/AD.2019.0127-32","doi-asserted-by":"crossref","unstructured":"Poynard T, Ratziu V, Charlotte F, Goodman Z, McHutchison J, Albrecht J (2001). Rates and risk factors of liver fibrosis progression in patients with chronic hepatitis C. J Hepatol, 34: 730-739.","DOI":"10.1016\/S0168-8278(00)00097-0"},{"key":"key-10.14336\/AD.2019.0127-33","doi-asserted-by":"crossref","unstructured":"Thabut D, Le Calvez S, Thibault V, Massard J, Munteanu M, Di Martino V, et al. (2006). Hepatitis C in 6,865 patients 65 yr or older: A severe and neglected curable disease? Am J Gastroenterol, 101: 1260-1267.","DOI":"10.1111\/j.1572-0241.2006.00556.x"},{"key":"key-10.14336\/AD.2019.0127-34","doi-asserted-by":"crossref","unstructured":"Davis GL, Alter MJ, El-Serag H, Poynard T, Jennings LW (2010). Aging of hepatitis C virus (HCV)-infected persons in the United States: a multiple cohort model of HCV prevalence and disease progression. Gastroenterology, 138: 513-521.","DOI":"10.1053\/j.gastro.2009.09.067"},{"key":"key-10.14336\/AD.2019.0127-35","doi-asserted-by":"crossref","unstructured":"Gracia-Sancho J, Marrone G, Fern\u00e1ndez-Iglesias A (2018). Hepatic microcirculation and mechanisms of portal hypertension. Nat Rev | Gastroenterol Hepatol, doi: .","DOI":"10.1038\/s41575-018-0097-3"},{"key":"key-10.14336\/AD.2019.0127-36","doi-asserted-by":"crossref","unstructured":"Canbay A, Taimr P, Torok N, Higuchi H, Friedman S, Gores GJ (2003). Apoptotic body engulfment by a human stellate cell line is profibrogenic. Lab Investig, 83: 655-663.","DOI":"10.1097\/01.LAB.0000069036.63405.5C"},{"key":"key-10.14336\/AD.2019.0127-37","doi-asserted-by":"crossref","unstructured":"Natori S, Higuchi H, Contreras P, Gores GJ (2003). The caspase inhibitor IDN-6556 prevents caspase activation and apoptosis in sinusoidal endothelial cells during liver preservation injury. Liver Transplant, 9: 278-284.","DOI":"10.1053\/jlts.2003.50019"},{"key":"key-10.14336\/AD.2019.0127-38","doi-asserted-by":"crossref","unstructured":"Mitchell SJ, Huizer-Pajkos A, Cogger VC, McLachlan AJ, Le Couteur DG, Jones B, et al. (2011). Age-related pseudocapillarization of the liver sinusoidal endothelium impairs the hepatic clearance of acetaminophen in rats. Journals Gerontol - Ser A Biol Sci, 66 A: 400-408.","DOI":"10.1093\/gerona\/glq221"},{"key":"key-10.14336\/AD.2019.0127-39","doi-asserted-by":"crossref","unstructured":"Fern\u00e1ndez-Iglesias A, Gracia-Sancho J (2017). How to Face Chronic Liver Disease: The Sinusoidal Perspective. Front Med, 4: 1-10.","DOI":"10.3389\/fmed.2017.00007"},{"key":"key-10.14336\/AD.2019.0127-40","doi-asserted-by":"crossref","unstructured":"Mahrouf-Yorgov M, de l\u2019Hortet AC, Cosson C, Slama A, Abdoun E, Guidotti J-E, et al. (2011). Increased Susceptibility to Liver Fibrosis with Age Is Correlated with an Altered Inflammatory Response. Rejuvenation Res, 14: 353-363.","DOI":"10.1089\/rej.2010.1146"},{"key":"key-10.14336\/AD.2019.0127-41","doi-asserted-by":"crossref","unstructured":"Wali M, Harrison RF, Gow PJ, Mutimer D (2002). Advancing donor liver age and rapid fibrosis progression following transplantation for hepatitis C. Gut, 51: 248-252.","DOI":"10.1136\/gut.51.2.248"},{"key":"key-10.14336\/AD.2019.0127-42","doi-asserted-by":"crossref","unstructured":"Tacke F (2017). Targeting hepatic macrophages to treat liver diseases. J Hepatol, 66: 1300-1312.","DOI":"10.1016\/j.jhep.2017.02.026"},{"key":"key-10.14336\/AD.2019.0127-43","doi-asserted-by":"crossref","unstructured":"Nieto N (2006). Oxidative-stress and IL-6 mediate the fibrogenic effects of rodent Kupffer cells on stellate cells. Hepatology, 44: 1487-1501.","DOI":"10.1002\/hep.21427"},{"key":"key-10.14336\/AD.2019.0127-44","doi-asserted-by":"crossref","unstructured":"Moctezuma-Vel\u00e1zquez C, Abraldes JG, Montano-Loza AJ (2018). The Use of Statins in Patients With Chronic Liver Disease and Cirrhosis. Curr Treat Options Gastroenterol, 16: 226-240.","DOI":"10.1007\/s11938-018-0180-4"},{"key":"key-10.14336\/AD.2019.0127-45","doi-asserted-by":"crossref","unstructured":"Rodr\u00edguez S, Raurell I, Torres-Arauz M, Garc\u00eda-Lezana T, Genesc\u00e0 J, Martell M (2017). A Nitric Oxide-Donating Statin Decreases Portal Pressure with a Better Toxicity Profile than Conventional Statins in Cirrhotic Rats. Sci Rep, 7: 1-12.","DOI":"10.1038\/srep40461"},{"key":"key-10.14336\/AD.2019.0127-46","doi-asserted-by":"crossref","unstructured":"Reagan-Shaw S, Nihal M, Ahmad N (2007). Dose translation from animal to human studies revisited. FASEB J, 22: 659-661.","DOI":"10.1096\/fj.07-9574LSF"},{"key":"key-10.14336\/AD.2019.0127-47","doi-asserted-by":"crossref","unstructured":"Briones AM, Rodr\u00edguez-Criado N, Hernanz R, Garc\u00eda-Redondo AB, Rodrigues-D\u00edez RR, Alonso MJ, et al. (2009). Atorvastatin prevents angiotensin II-induced vascular remodeling and oxidative stress. Hypertension, 54: 142-149.","DOI":"10.1161\/HYPERTENSIONAHA.109.133710"}],"container-title":["Aging and disease"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.aginganddisease.org\/fileup\/2152-5250\/PDF\/ad-0-0-0-1902181946-1.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,7,29]],"date-time":"2021-07-29T03:20:47Z","timestamp":1627528847000},"score":1,"resource":{"primary":{"URL":"http:\/\/www.aginganddisease.org\/EN\/10.14336\/AD.2019.0127"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019]]},"references-count":47,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.14336\/ad.2019.0127","relation":{},"ISSN":["2152-5250"],"issn-type":[{"value":"2152-5250","type":"print"}],"subject":[],"published":{"date-parts":[[2019]]}}}