Shawer, H, Norman, K, Cheng, CW orcid.org/0000-0002-2873-0828 et al. (3 more authors) (2021) ORAI1 Ca2+ channel as a therapeutic target in pathological vascular remodelling. Frontiers in Cell and Developmental Biology, 9. 653812. ISSN 2296-634X
Abstract
Cardiovascular disease (CVD) defines the conditions affecting the heart and blood vessels. CVD is currently the leading cause of global mortality, accounting for an estimated 17 million deaths annually (WHO, 2017). This figure is anticipated to rise as the prevalence in low and middle-income countries increases. CVD is associated with classical risk factors, including obesity (Poirier et al., 2006), smoking (Keto et al., 2016), family history (Dorairaj and Panniyammakal, 2012; Jeemon et al., 2017), and diabetes (Rydén et al., 2013; Shah et al., 2015). Atherosclerotic CVD (e.g., ischaemic heart disease, peripheral arterial disease, cerebrovascular disease, renovascular disease), pulmonary hypertension and aneurysm formation have all been associated with pathological remodelling behaviour of the native vascular smooth muscle cells (VSMC) within the arterial wall. Similarly, failure of surgical revascularisation to treat atherosclerotic CVD lesions (bypass grafting with autologous vein or prosthetic graft) or percutaneous coronary intervention/peripheral artery endovascular intervention (angioplasty+/−stenting) is associated with neointimal hyperplasia (NIH) which is also a manifestation of pathological vascular remodelling. The ability to selectively inhibit such pathological remodelling of VSMC is therefore considered to be a potentially fruitful therapeutic strategy across this range of cardiovascular pathologies. In order to achieve this, an identifiable, specific, druggable target is required. In this review we present an update on the evidence supporting the ORAI1 Ca2+ channel as a potential therapeutic target and the current status of inhibitor development. The focus is on atherosclerotic CVD and NIH as little evidence exists regarding aneurysm disease in this context and we recently reviewed the evidence supporting ORAI1 as a target in pulmonary hypertension (Rode et al., 2018).
Metadata
Item Type: | Article |
---|---|
Authors/Creators: |
|
Copyright, Publisher and Additional Information: | © 2021 Shawer, Norman, Cheng, Foster, Beech and Bailey. 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. |
Keywords: | ORAI1; STIM1; Calcium; Vascular remodelling; Store operated calcium entry (SOCE); vascular smooth muscle; Pharmacology |
Dates: |
|
Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Engineering & Physical Sciences (Leeds) > School of Chemistry (Leeds) > Organic Chemistry (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Cardiovascular and Metabolic Medicine (LICAMM) > Discovery & Translational Science Dept (Leeds) |
Funding Information: | Funder Grant number British Heart Foundation FS/18/12/33270 British Heart Foundation FS/17/66/33480 |
Depositing User: | Symplectic Publications |
Date Deposited: | 11 Mar 2021 16:12 |
Last Modified: | 25 Jun 2023 22:36 |
Status: | Published |
Publisher: | Frontiers Media |
Identification Number: | 10.3389/fcell.2021.653812 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:171947 |