Cargando…
Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation
Liver fibrosis is associated with arterial calcification (AC). Since the liver is a source of inorganic pyrophosphate (PPi), an anti-calcifying compound, we investigated the relationship between plasma PPi ([PPi]pl), liver fibrosis, liver function, AC, and the hepatic expression of genes regulating...
Autores principales: | , , , , , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312703/ https://www.ncbi.nlm.nih.gov/pubmed/35884801 http://dx.doi.org/10.3390/biomedicines10071496 |
_version_ | 1784753899687641088 |
---|---|
author | Laurain, Audrey Rubera, Isabelle Razzouk-Cadet, Micheline Bonnafous, Stéphanie Albuquerque, Miguel Paradis, Valérie Patouraux, Stéphanie Duranton, Christophe Lesaux, Olivier Lefthériotis, Georges Tran, Albert Anty, Rodolphe Gual, Philippe Iannelli, Antonio Favre, Guillaume |
author_facet | Laurain, Audrey Rubera, Isabelle Razzouk-Cadet, Micheline Bonnafous, Stéphanie Albuquerque, Miguel Paradis, Valérie Patouraux, Stéphanie Duranton, Christophe Lesaux, Olivier Lefthériotis, Georges Tran, Albert Anty, Rodolphe Gual, Philippe Iannelli, Antonio Favre, Guillaume |
author_sort | Laurain, Audrey |
collection | PubMed |
description | Liver fibrosis is associated with arterial calcification (AC). Since the liver is a source of inorganic pyrophosphate (PPi), an anti-calcifying compound, we investigated the relationship between plasma PPi ([PPi]pl), liver fibrosis, liver function, AC, and the hepatic expression of genes regulating PPi homeostasis. To that aim, we compared [PPi]pl before liver transplantation (LT) and 3 months after LT. We also assessed the expression of four key regulators of PPi in liver tissues and established correlations between AC, and scores of liver fibrosis and liver failure in these patients. LT candidates with various liver diseases were included. AC scores were assessed in coronary arteries, abdominal aorta, and aortic valves. Liver fibrosis was evaluated on liver biopsies and from non-invasive tests (FIB-4 and APRI scores). Liver functions were assessed by measuring serum albumin, ALBI, MELD, and Pugh–Child scores. An enzymatic assay was used to dose [PPi]pl. A group of patients without liver alterations from a previous cohort provided a control group. Gene expression assays were performed with mRNA extracted from liver biopsies and compared between LT recipients and the control individuals. [PPi]pl negatively correlated with APRI (r = −0.57, p = 0.001, n = 29) and FIB-4 (r = −0.47, p = 0.006, n = 29) but not with interstitial fibrosis index from liver biopsies (r = 0.07, p = 0.40, n = 16). Serum albumin positively correlated with [PPi]pl (r = 0.71; p < 0.0001, n = 20). ALBI, MELD, and Pugh–Child scores correlated negatively with [PPi]pl (r = −0.60, p = 0.0005; r = −0.56, p = 0.002; r = −0.41, p = 0.02, respectively, with n = 20). Liver fibrosis assessed on liver biopsies by FIB-4 and by APRI positively correlated with coronary AC (r = 0.51, p = 0.02, n = 16; r = 0.58, p = 0.009, n = 20; r = 0.41, p = 0.04, n = 20, respectively) and with abdominal aorta AC (r = 0.50, p = 0.02, n = 16; r = 0.67, p = 0.002, n = 20; r = 0.61, p = 0.04, n = 20, respectively). FIB-4 also positively correlated with aortic valve calcification (r = 0.40, p = 0.046, n = 20). The key regulator genes of PPi production in liver were lower in patients undergoing liver transplantation as compared to controls. Three months after surgery, serum albumin levels were restored to physiological levels (40 [37–44] vs. 35 [30–40], p = 0.009) and [PPi]pl was normalized (1.40 [1.07–1.86] vs. 0.68 [0.53–0.80] µmol/L, p = 0.0005, n = 12). Liver failure and/or fibrosis correlated with AC in several arterial beds and were associated with low plasma PPi and dysregulation of key proteins involved in PPi homeostasis. Liver transplantation normalized these parameters. |
format | Online Article Text |
id | pubmed-9312703 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-93127032022-07-26 Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation Laurain, Audrey Rubera, Isabelle Razzouk-Cadet, Micheline Bonnafous, Stéphanie Albuquerque, Miguel Paradis, Valérie Patouraux, Stéphanie Duranton, Christophe Lesaux, Olivier Lefthériotis, Georges Tran, Albert Anty, Rodolphe Gual, Philippe Iannelli, Antonio Favre, Guillaume Biomedicines Article Liver fibrosis is associated with arterial calcification (AC). Since the liver is a source of inorganic pyrophosphate (PPi), an anti-calcifying compound, we investigated the relationship between plasma PPi ([PPi]pl), liver fibrosis, liver function, AC, and the hepatic expression of genes regulating PPi homeostasis. To that aim, we compared [PPi]pl before liver transplantation (LT) and 3 months after LT. We also assessed the expression of four key regulators of PPi in liver tissues and established correlations between AC, and scores of liver fibrosis and liver failure in these patients. LT candidates with various liver diseases were included. AC scores were assessed in coronary arteries, abdominal aorta, and aortic valves. Liver fibrosis was evaluated on liver biopsies and from non-invasive tests (FIB-4 and APRI scores). Liver functions were assessed by measuring serum albumin, ALBI, MELD, and Pugh–Child scores. An enzymatic assay was used to dose [PPi]pl. A group of patients without liver alterations from a previous cohort provided a control group. Gene expression assays were performed with mRNA extracted from liver biopsies and compared between LT recipients and the control individuals. [PPi]pl negatively correlated with APRI (r = −0.57, p = 0.001, n = 29) and FIB-4 (r = −0.47, p = 0.006, n = 29) but not with interstitial fibrosis index from liver biopsies (r = 0.07, p = 0.40, n = 16). Serum albumin positively correlated with [PPi]pl (r = 0.71; p < 0.0001, n = 20). ALBI, MELD, and Pugh–Child scores correlated negatively with [PPi]pl (r = −0.60, p = 0.0005; r = −0.56, p = 0.002; r = −0.41, p = 0.02, respectively, with n = 20). Liver fibrosis assessed on liver biopsies by FIB-4 and by APRI positively correlated with coronary AC (r = 0.51, p = 0.02, n = 16; r = 0.58, p = 0.009, n = 20; r = 0.41, p = 0.04, n = 20, respectively) and with abdominal aorta AC (r = 0.50, p = 0.02, n = 16; r = 0.67, p = 0.002, n = 20; r = 0.61, p = 0.04, n = 20, respectively). FIB-4 also positively correlated with aortic valve calcification (r = 0.40, p = 0.046, n = 20). The key regulator genes of PPi production in liver were lower in patients undergoing liver transplantation as compared to controls. Three months after surgery, serum albumin levels were restored to physiological levels (40 [37–44] vs. 35 [30–40], p = 0.009) and [PPi]pl was normalized (1.40 [1.07–1.86] vs. 0.68 [0.53–0.80] µmol/L, p = 0.0005, n = 12). Liver failure and/or fibrosis correlated with AC in several arterial beds and were associated with low plasma PPi and dysregulation of key proteins involved in PPi homeostasis. Liver transplantation normalized these parameters. MDPI 2022-06-24 /pmc/articles/PMC9312703/ /pubmed/35884801 http://dx.doi.org/10.3390/biomedicines10071496 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Laurain, Audrey Rubera, Isabelle Razzouk-Cadet, Micheline Bonnafous, Stéphanie Albuquerque, Miguel Paradis, Valérie Patouraux, Stéphanie Duranton, Christophe Lesaux, Olivier Lefthériotis, Georges Tran, Albert Anty, Rodolphe Gual, Philippe Iannelli, Antonio Favre, Guillaume Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation |
title | Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation |
title_full | Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation |
title_fullStr | Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation |
title_full_unstemmed | Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation |
title_short | Arterial Calcifications in Patients with Liver Cirrhosis Are Linked to Hepatic Deficiency of Pyrophosphate Production Restored by Liver Transplantation |
title_sort | arterial calcifications in patients with liver cirrhosis are linked to hepatic deficiency of pyrophosphate production restored by liver transplantation |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9312703/ https://www.ncbi.nlm.nih.gov/pubmed/35884801 http://dx.doi.org/10.3390/biomedicines10071496 |
work_keys_str_mv | AT laurainaudrey arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT ruberaisabelle arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT razzoukcadetmicheline arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT bonnafousstephanie arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT albuquerquemiguel arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT paradisvalerie arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT patourauxstephanie arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT durantonchristophe arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT lesauxolivier arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT leftheriotisgeorges arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT tranalbert arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT antyrodolphe arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT gualphilippe arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT iannelliantonio arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation AT favreguillaume arterialcalcificationsinpatientswithlivercirrhosisarelinkedtohepaticdeficiencyofpyrophosphateproductionrestoredbylivertransplantation |