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The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders

Chronic obesity is associated with metabolic imbalance leading to diabetes, dyslipidemia, and cardiovascular diseases (CVDs), in which inflammation is caused by exposure to inflammatory stimuli, such as accumulating sphingolipid ceramides or intracellular stress. This inflammatory response is likely...

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Autores principales: Geesala, Ramasatyaveni, Issuree, Priya D., Maretzky, Thorsten
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732453/
https://www.ncbi.nlm.nih.gov/pubmed/33330676
http://dx.doi.org/10.3389/fcvm.2020.612808
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author Geesala, Ramasatyaveni
Issuree, Priya D.
Maretzky, Thorsten
author_facet Geesala, Ramasatyaveni
Issuree, Priya D.
Maretzky, Thorsten
author_sort Geesala, Ramasatyaveni
collection PubMed
description Chronic obesity is associated with metabolic imbalance leading to diabetes, dyslipidemia, and cardiovascular diseases (CVDs), in which inflammation is caused by exposure to inflammatory stimuli, such as accumulating sphingolipid ceramides or intracellular stress. This inflammatory response is likely to be prolonged by the effects of dietary and blood cholesterol, thereby leading to chronic low-grade inflammation and endothelial dysfunction. Elevated levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF) are predictive of CVDs and have been widely studied for potential therapeutic strategies. The release of TNF is controlled by a disintegrin and metalloprotease (ADAM) 17 and both are positively associated with CVDs. ADAM17 also cleaves most of the ligands of the epidermal growth factor receptor (EGFR) which have been associated with hypertension, atherogenesis, vascular dysfunction, and cardiac remodeling. The inactive rhomboid protein 2 (iRhom2) regulates the ADAM17-dependent shedding of TNF in immune cells. In addition, iRhom2 also regulates the ADAM17-mediated cleavage of EGFR ligands such as amphiregulin and heparin-binding EGF-like growth factor. Targeting iRhom2 has recently become a possible alternative therapeutic strategy in chronic inflammatory diseases such as lupus nephritis and rheumatoid arthritis. However, what role this intriguing interacting partner of ADAM17 plays in the vasculature and how it functions in the pathologies of obesity and associated CVDs, are exciting questions that are only beginning to be elucidated. In this review, we discuss the role of iRhom2 in cardiovascular-related pathologies such as atherogenesis and obesity by providing an evaluation of known iRhom2-dependent cellular and inflammatory pathways.
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spelling pubmed-77324532020-12-15 The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders Geesala, Ramasatyaveni Issuree, Priya D. Maretzky, Thorsten Front Cardiovasc Med Cardiovascular Medicine Chronic obesity is associated with metabolic imbalance leading to diabetes, dyslipidemia, and cardiovascular diseases (CVDs), in which inflammation is caused by exposure to inflammatory stimuli, such as accumulating sphingolipid ceramides or intracellular stress. This inflammatory response is likely to be prolonged by the effects of dietary and blood cholesterol, thereby leading to chronic low-grade inflammation and endothelial dysfunction. Elevated levels of pro-inflammatory cytokines such as tumor necrosis factor (TNF) are predictive of CVDs and have been widely studied for potential therapeutic strategies. The release of TNF is controlled by a disintegrin and metalloprotease (ADAM) 17 and both are positively associated with CVDs. ADAM17 also cleaves most of the ligands of the epidermal growth factor receptor (EGFR) which have been associated with hypertension, atherogenesis, vascular dysfunction, and cardiac remodeling. The inactive rhomboid protein 2 (iRhom2) regulates the ADAM17-dependent shedding of TNF in immune cells. In addition, iRhom2 also regulates the ADAM17-mediated cleavage of EGFR ligands such as amphiregulin and heparin-binding EGF-like growth factor. Targeting iRhom2 has recently become a possible alternative therapeutic strategy in chronic inflammatory diseases such as lupus nephritis and rheumatoid arthritis. However, what role this intriguing interacting partner of ADAM17 plays in the vasculature and how it functions in the pathologies of obesity and associated CVDs, are exciting questions that are only beginning to be elucidated. In this review, we discuss the role of iRhom2 in cardiovascular-related pathologies such as atherogenesis and obesity by providing an evaluation of known iRhom2-dependent cellular and inflammatory pathways. Frontiers Media S.A. 2020-11-24 /pmc/articles/PMC7732453/ /pubmed/33330676 http://dx.doi.org/10.3389/fcvm.2020.612808 Text en Copyright © 2020 Geesala, Issuree and Maretzky. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Cardiovascular Medicine
Geesala, Ramasatyaveni
Issuree, Priya D.
Maretzky, Thorsten
The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders
title The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders
title_full The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders
title_fullStr The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders
title_full_unstemmed The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders
title_short The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders
title_sort role of irhom2 in metabolic and cardiovascular-related disorders
topic Cardiovascular Medicine
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7732453/
https://www.ncbi.nlm.nih.gov/pubmed/33330676
http://dx.doi.org/10.3389/fcvm.2020.612808
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