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Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies
- Source :
- Pharmacological reviews. 73(3)
- Publication Year :
- 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. SIGNIFICANCE STATEMENT: The endothelium was initially considered to be a semipermeable biomechanical barrier and gatekeeper of vascular health. In recent decades, a deepened understanding of the biological functions of the endothelium has led to its recognition as a ubiquitous tissue regulating vascular tone, cell behavior, innate immunity, cell-cell interactions, and cell metabolism in the vessel wall. Endothelial dysfunction is the hallmark of cardiovascular, metabolic, and emerging infectious diseases. Pharmacotherapies targeting endothelial dysfunction have potential for treatment of cardiovascular and many other diseases.
- Subjects :
- 0301 basic medicine
Endothelium
Angiogenesis
Inflammation
Vasodilation
Bioinformatics
03 medical and health sciences
0302 clinical medicine
Drug Discovery
medicine
Humans
Molecular Targeted Therapy
Endothelial dysfunction
Pharmacology
business.industry
SARS-CoV-2
COVID-19
Cardiovascular Agents
medicine.disease
Atherosclerosis
COVID-19 Drug Treatment
Endothelial stem cell
030104 developmental biology
medicine.anatomical_structure
Cardiovascular Diseases
Hemostasis
Cardiovascular agent
Molecular Medicine
Endothelium, Vascular
medicine.symptom
business
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 15210081
- Volume :
- 73
- Issue :
- 3
- Database :
- OpenAIRE
- Journal :
- Pharmacological reviews
- Accession number :
- edsair.doi.dedup.....0288b9677bf5d826c46d6ff676265ca8