Journal article
Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies
Pharmacological Reviews, Vol.73(3), pp.924-967
2021
Abstract
The endothelium, a cellular monolayer lining the blood vessel wall, plays a critical role in maintaining multiorgan health and homeostasis. Endothelial functions in health include dynamic maintenance of vascular tone, angiogenesis, hemostasis, and the provision of an antioxidant, anti-inflammatory, and antithrombotic interface. Dysfunction of the vascular endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, and endothelial cell senescence. Recent studies have implicated altered endothelial cell metabolism and endothelial-to-mesenchymal transition as new features of endothelial dysfunction. Endothelial dysfunction is regarded as a hallmark of many diverse human panvascular diseases, including atherosclerosis, hypertension, and diabetes. Endothelial dysfunction has also been implicated in severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive drugs, and antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors and interleukin 1β monoclonal antibodies, counter endothelial dysfunction as part of their clinical benefits. The regulation of endothelial dysfunction by noncoding RNAs has provided novel insights into these newly described regulators of endothelial dysfunction, thus yielding potential new therapeutic approaches. Altogether, a better understanding of the versatile (dys)functions of endothelial cells will not only deepen our comprehension of human diseases but also accelerate effective therapeutic drug discovery. In this review, we provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of endothelial dysfunction, and identify pathways to effective targeted therapies.
Details
- Title
- Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies
- Authors
- Suowen Xu (Author) - University of Science and Technology of ChinaIqra Ilyas (Author) - University of Science and Technology of ChinaPeter J Little (Author) - University of the Sunshine CoastHong Li (Author) - University of Science and Technology of ChinaDanielle Kamato (Author) - University of QueenslandXueying Zheng (Author) - University of Science and Technology of ChinaSihui Luo (Author) - University of Science and Technology of ChinaZhuoming Li (Author) - University of Science and Technology of ChinaPeiqing Liu (Author) - University of Science and Technology of ChinaJihong Han (Author) - University of Science and Technology of ChinaIan C Harding (Author) - University of Science and Technology of ChinaEno E Ebong (Author) - University of Science and Technology of ChinaScott J Cameron (Author) - University of Science and Technology of ChinaAlastair G Stewart (Author) - University of Science and Technology of ChinaJianping Weng (Author) - University of Science and Technology of China
- Publication details
- Pharmacological Reviews, Vol.73(3), pp.924-967
- Publisher
- American Society for Pharmacology and Experimental Therapeutics
- DOI
- 10.1124/pharmrev.120.000096
- ISSN
- 1521-0081
- Organisation Unit
- University of the Sunshine Coast, Queensland; School of Health and Behavioural Sciences - Legacy; School of Health
- Language
- English
- Record Identifier
- 99543308102621
- Output Type
- Journal article
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- Domestic collaboration
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- Web Of Science research areas
- Pharmacology & Pharmacy
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