Journal article
The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders
Frontiers in cardiovascular medicine, Vol.7, pp.612808-612808
11/24/2020
DOI: 10.3389/fcvm.2020.612808
PMCID: PMC7732453
PMID: 33330676
Abstract
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.
Details
- Title: Subtitle
- The Role of iRhom2 in Metabolic and Cardiovascular-Related Disorders
- Creators
- Ramasatyaveni Geesala - University of IowaPriya D. Issuree - Roy J. and Lucille A. Carver College of MedicineThorsten Maretzky - Roy J. and Lucille A. Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Frontiers in cardiovascular medicine, Vol.7, pp.612808-612808
- DOI
- 10.3389/fcvm.2020.612808
- PMID
- 33330676
- PMCID
- PMC7732453
- NLM abbreviation
- Front Cardiovasc Med
- ISSN
- 2297-055X
- eISSN
- 2297-055X
- Publisher
- Frontiers Media Sa
- Number of pages
- 10
- Grant note
- Roy J. and Lucille A. Carver College of Medicine ACS-IRG-18-16543 / American Cancer Society Carver Trust Collaborative Pilot Grant through the University of Iowa
- Language
- English
- Date published
- 11/24/2020
- Academic Unit
- Infectious Diseases; Internal Medicine
- Record Identifier
- 9984360149602771
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