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The Circulating GRP78/BiP Is a Marker of Metabolic Diseases and Atherosclerosis: Bringing Endoplasmic Reticulum Stress into the Clinical Scenario

Background: Glucose-regulated protein 78/Binding immunoglobulin protein (GRP78/BiP) is a protein associated with endoplasmic reticulum stress and is upregulated by metabolic alterations at the tissue-level, such as hypoxia or glucose deprivation, and it is hyper-expressed in fat tissue of obese indi...

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Autores principales: Girona, Josefa, Rodríguez-Borjabad, Cèlia, Ibarretxe, Daiana, Vallvé, Joan-Carles, Ferré, Raimon, Heras, Mercedes, Rodríguez-Calvo, Ricardo, Guaita-Esteruelas, Sandra, Martínez-Micaelo, Neus, Plana, Núria, Masana, Lluís
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912434/
https://www.ncbi.nlm.nih.gov/pubmed/31717752
http://dx.doi.org/10.3390/jcm8111793
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author Girona, Josefa
Rodríguez-Borjabad, Cèlia
Ibarretxe, Daiana
Vallvé, Joan-Carles
Ferré, Raimon
Heras, Mercedes
Rodríguez-Calvo, Ricardo
Guaita-Esteruelas, Sandra
Martínez-Micaelo, Neus
Plana, Núria
Masana, Lluís
author_facet Girona, Josefa
Rodríguez-Borjabad, Cèlia
Ibarretxe, Daiana
Vallvé, Joan-Carles
Ferré, Raimon
Heras, Mercedes
Rodríguez-Calvo, Ricardo
Guaita-Esteruelas, Sandra
Martínez-Micaelo, Neus
Plana, Núria
Masana, Lluís
author_sort Girona, Josefa
collection PubMed
description Background: Glucose-regulated protein 78/Binding immunoglobulin protein (GRP78/BiP) is a protein associated with endoplasmic reticulum stress and is upregulated by metabolic alterations at the tissue-level, such as hypoxia or glucose deprivation, and it is hyper-expressed in fat tissue of obese individuals. Objective: To investigate the role of the GRP78/BiP level as a metabolic and vascular disease biomarker in patients with type 2 diabetes (DM), obesity and metabolic syndrome (MS). Methods: Four hundred and five patients were recruited, of whom 52.5% were obese, 72.8% had DM, and 78.6% had MS. The intimae media thickness (cIMT) was assessed by ultrasonography. The plasma GRP78/BiP concentration was determined, and its association with metabolic and vascular parameters was assessed. Circulating GRP78/BiP was also prospectively measured in 30 DM patients before and after fenofibrate/niacin treatment and 30 healthy controls. Results: In the cross-sectional study, the GRP78/BiP level was significantly higher in the patients with obesity, DM, and MS. Age-, gender- and BMI-adjusted GRP78/BiP was directly associated with LDL-cholesterol, non-HDL-cholesterol, triglycerides, apoB, and cIMT. GRP78/BiP was positively associated to carotid plaque presence in the adjusted model, irrespective of obesity, DM and MS. In the prospective study, nicotinic acid treatment produced a significant reduction in the GRP78/BiP levels that was not observed with fenofibrate. Conclusions: GRP78/BiP plasma concentrations are increased in patients with both metabolic derangements and subclinical atherosclerosis. GRP78/BiP could be a useful marker of metabolic and cardiovascular risk.
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spelling pubmed-69124342020-01-02 The Circulating GRP78/BiP Is a Marker of Metabolic Diseases and Atherosclerosis: Bringing Endoplasmic Reticulum Stress into the Clinical Scenario Girona, Josefa Rodríguez-Borjabad, Cèlia Ibarretxe, Daiana Vallvé, Joan-Carles Ferré, Raimon Heras, Mercedes Rodríguez-Calvo, Ricardo Guaita-Esteruelas, Sandra Martínez-Micaelo, Neus Plana, Núria Masana, Lluís J Clin Med Article Background: Glucose-regulated protein 78/Binding immunoglobulin protein (GRP78/BiP) is a protein associated with endoplasmic reticulum stress and is upregulated by metabolic alterations at the tissue-level, such as hypoxia or glucose deprivation, and it is hyper-expressed in fat tissue of obese individuals. Objective: To investigate the role of the GRP78/BiP level as a metabolic and vascular disease biomarker in patients with type 2 diabetes (DM), obesity and metabolic syndrome (MS). Methods: Four hundred and five patients were recruited, of whom 52.5% were obese, 72.8% had DM, and 78.6% had MS. The intimae media thickness (cIMT) was assessed by ultrasonography. The plasma GRP78/BiP concentration was determined, and its association with metabolic and vascular parameters was assessed. Circulating GRP78/BiP was also prospectively measured in 30 DM patients before and after fenofibrate/niacin treatment and 30 healthy controls. Results: In the cross-sectional study, the GRP78/BiP level was significantly higher in the patients with obesity, DM, and MS. Age-, gender- and BMI-adjusted GRP78/BiP was directly associated with LDL-cholesterol, non-HDL-cholesterol, triglycerides, apoB, and cIMT. GRP78/BiP was positively associated to carotid plaque presence in the adjusted model, irrespective of obesity, DM and MS. In the prospective study, nicotinic acid treatment produced a significant reduction in the GRP78/BiP levels that was not observed with fenofibrate. Conclusions: GRP78/BiP plasma concentrations are increased in patients with both metabolic derangements and subclinical atherosclerosis. GRP78/BiP could be a useful marker of metabolic and cardiovascular risk. MDPI 2019-10-26 /pmc/articles/PMC6912434/ /pubmed/31717752 http://dx.doi.org/10.3390/jcm8111793 Text en © 2019 by the authors. 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 (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Girona, Josefa
Rodríguez-Borjabad, Cèlia
Ibarretxe, Daiana
Vallvé, Joan-Carles
Ferré, Raimon
Heras, Mercedes
Rodríguez-Calvo, Ricardo
Guaita-Esteruelas, Sandra
Martínez-Micaelo, Neus
Plana, Núria
Masana, Lluís
The Circulating GRP78/BiP Is a Marker of Metabolic Diseases and Atherosclerosis: Bringing Endoplasmic Reticulum Stress into the Clinical Scenario
title The Circulating GRP78/BiP Is a Marker of Metabolic Diseases and Atherosclerosis: Bringing Endoplasmic Reticulum Stress into the Clinical Scenario
title_full The Circulating GRP78/BiP Is a Marker of Metabolic Diseases and Atherosclerosis: Bringing Endoplasmic Reticulum Stress into the Clinical Scenario
title_fullStr The Circulating GRP78/BiP Is a Marker of Metabolic Diseases and Atherosclerosis: Bringing Endoplasmic Reticulum Stress into the Clinical Scenario
title_full_unstemmed The Circulating GRP78/BiP Is a Marker of Metabolic Diseases and Atherosclerosis: Bringing Endoplasmic Reticulum Stress into the Clinical Scenario
title_short The Circulating GRP78/BiP Is a Marker of Metabolic Diseases and Atherosclerosis: Bringing Endoplasmic Reticulum Stress into the Clinical Scenario
title_sort circulating grp78/bip is a marker of metabolic diseases and atherosclerosis: bringing endoplasmic reticulum stress into the clinical scenario
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6912434/
https://www.ncbi.nlm.nih.gov/pubmed/31717752
http://dx.doi.org/10.3390/jcm8111793
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