Effects of aging on liver microcirculatory function and sinusoidal phenotype.
Por:
Maeso-Díaz R, Ortega-Ribera M, Fernández-Iglesias A, Hide D, Munoz, L, Hessheimer AJ, Vila S, Frances R, Fondevila C, Albillos A, Peralta C, Bosch J, Tacke F, Cogger VC and Gracia-Sancho J
Publicada:
1 dic 2018
Resumen:
The socioeconomic and medical improvements of the last decades have led to a relevant increase in the median age of worldwide population. Although numerous studies described the impact of aging in different organs and the systemic vasculature, relatively little is known about liver function and hepatic microcirculatory status in the elderly. In this study, we aimed at characterizing the phenotype of the aged liver in a rat model of healthy aging, particularly focusing on the microcirculatory function and the molecular status of each hepatic cell type in the sinusoid. Moreover, major findings of the study were validated in young and aged human livers. Our results demonstrate that healthy aging is associated with hepatic and sinusoidal dysfunction, with elevated hepatic vascular resistance and increased portal pressure. Underlying mechanisms of such hemodynamic disturbances included typical molecular changes in the cells of the hepatic sinusoid and deterioration in hepatocyte function. In a specific manner, liver sinusoidal endothelial cells presented a dysfunctional phenotype with diminished vasodilators synthesis, hepatic macrophages exhibited a proinflammatory state, while hepatic stellate cells spontaneously displayed an activated profile. In an important way, major changes in sinusoidal markers were confirmed in livers from aged humans. In conclusion, our study demonstrates for the first time that aging is accompanied by significant liver sinusoidal deregulation suggesting enhanced sinusoidal vulnerability to chronic or acute injuries.
Filiaciones:
Maeso-Díaz R:
Univ Barcelona, IDIBAPS Biomed Res Inst, Liver Vasc Biol Res Grp, Barcelona Hepat Hemodynam Lab,Med Sch, Barcelona, Spain
Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS Biomedical Research Institute, University of Barcelona Medical School, Barcelona, Spain
Ortega-Ribera M:
Univ Barcelona, IDIBAPS Biomed Res Inst, Liver Vasc Biol Res Grp, Barcelona Hepat Hemodynam Lab,Med Sch, Barcelona, Spain
Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS Biomedical Research Institute, University of Barcelona Medical School, Barcelona, Spain
Fernández-Iglesias A:
Univ Barcelona, IDIBAPS Biomed Res Inst, Liver Vasc Biol Res Grp, Barcelona Hepat Hemodynam Lab,Med Sch, Barcelona, Spain
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS Biomedical Research Institute, University of Barcelona Medical School, Barcelona, Spain
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
Hide D:
Univ Barcelona, IDIBAPS Biomed Res Inst, Liver Vasc Biol Res Grp, Barcelona Hepat Hemodynam Lab,Med Sch, Barcelona, Spain
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS Biomedical Research Institute, University of Barcelona Medical School, Barcelona, Spain
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
Munoz, L:
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
Univ Alcala De Henares, Dept Med, Immune Syst Dis Lab, Alcala De Henares, Spain
Hessheimer AJ:
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
Hosp Clin Barcelona, Liver Surg & Transplantat Unit, IDIBAPS, Barcelona, Spain
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
Liver Surgery and Transplantation Unit, IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain
Vila S:
Univ Barcelona, IDIBAPS Biomed Res Inst, Liver Vasc Biol Res Grp, Barcelona Hepat Hemodynam Lab,Med Sch, Barcelona, Spain
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS Biomedical Research Institute, University of Barcelona Medical School, Barcelona, Spain
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
Frances R:
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
Inmunobiologia de la traslocación bacteriana_Fdn FISABIO, Inst Invest Sanit & Biomed Alicante ISABIAL, Alicante, Spain
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL - Fundación FISABIO), Alicante, Spain
Fondevila C:
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
Hosp Clin Barcelona, Liver Surg & Transplantat Unit, IDIBAPS, Barcelona, Spain
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
Liver Surgery and Transplantation Unit, IDIBAPS, Hospital Clínic de Barcelona, Barcelona, Spain
Albillos A:
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
Univ Alcala De Henares, Dept Med, Immune Syst Dis Lab, Alcala De Henares, Spain
Univ Alcala De Henares, Hosp Univ Ramon y Cajal, Dept Gastroenterol & Hepatol, IRYCIS, Madrid, Spain
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
Immune System Diseases Laboratory, Department of Medicine, University of Alcalá, Alcalá de Henares, Spain
Department of Gastroenterology and Hepatology, Hospital Universitario Ramón y Cajal, IRYCIS, Universidad de Alcalá, Madrid, Spain
Peralta C:
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
IDIBAPS, Protect Strategies Hepat Ischemia Reperfus Grp, Barcelona, Spain
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
Protective Strategies Against Hepatic Ischemia-Reperfusion Group, IDIBAPS, Barcelona, Spain
Bosch J:
Univ Barcelona, IDIBAPS Biomed Res Inst, Liver Vasc Biol Res Grp, Barcelona Hepat Hemodynam Lab,Med Sch, Barcelona, Spain
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
Bern Univ, Dept Biomed Res, Hepatol, Inselspital, Bern, Switzerland
Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS Biomedical Research Institute, University of Barcelona Medical School, Barcelona, Spain
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
Hepatology, Department of Biomedical Research, Inselspital, Bern University, Bern, Switzerland
Tacke F:
Univ Hosp Aachen, Dept Med 3, Aachen, Germany
Dept of Medicine III, University Hospital Aachen, Aachen, Germany
Cogger VC:
Univ Sydney, Ctr Educ & Res Ageing, Sydney, NSW, Australia
Univ Sydney, ANZAC Res Inst, Sydney, NSW, Australia
Concord Hosp, Sydney, NSW, Australia
Centre for Education and Research on Ageing ANZAC Research Institute, University of Sydney and Concord Hospital, Sydney, Australia
Gracia-Sancho J:
Univ Barcelona, IDIBAPS Biomed Res Inst, Liver Vasc Biol Res Grp, Barcelona Hepat Hemodynam Lab,Med Sch, Barcelona, Spain
Biomed Res Networking Ctr Hepat & Digest Dis CIBE, Madrid, Spain
Bern Univ, Dept Biomed Res, Hepatol, Inselspital, Bern, Switzerland
Liver Vascular Biology Research Group, Barcelona Hepatic Hemodynamic Laboratory, IDIBAPS Biomedical Research Institute, University of Barcelona Medical School, Barcelona, Spain
Biomedical Research Networking Center in Hepatic and Digestive Diseases (CIBEREHD), Madrid, Spain
Hepatology, Department of Biomedical Research, Inselspital, Bern University, Bern, Switzerland
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