Journal ArticleDOI
Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies.
Suowen Xu,Iqra Ilyas,Peter J. Little,Hong Li,Danielle Kamato,Xueying Zheng,Sihui Luo,Zhuoming Li,Peiqing Liu,Jihong Han,Ian C. Harding,Eno E. Ebong,Scott J. Cameron,Alastair G. Stewart,Jianping Weng +14 more
TLDR
In this article, the authors provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of the endothelial dysfunction, and identify pathways to effective targeted therapies.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.read more
Citations
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Journal ArticleDOI
Endothelial Dysfunction in Hypertension: Current Concepts and Clinical Implications
TL;DR: The release of extracellular vesicles by neighboring cells in the vascular wall has emerged as an important regulator of endothelial function and with potential antihypertensive properties and beneficial effects by counteracting the hypertension mediated organ damage.
Journal ArticleDOI
Resveratrol and endothelial function: A literature review.
Negin Parsamanesh,Arghavan Asghari,Saeed Sardari,Aida Tasbandi,Tannaz Jamialahmadi,Suowen Xu,Amirhossein Sahebkar +6 more
TL;DR: In this article, an updated review addressing pharmacological effects and molecular targets of RSV in maintaining endothelial function, and the potential of this phytochemical for endothelial dysfunction-associated disorders is presented.
Journal ArticleDOI
Endothelial dysfunction in COVID-19: an overview of evidence, biomarkers, mechanisms and potential therapies
TL;DR: In this article , a review of biomarkers associated with endothelial cell activation in COVID-19 and mechanistic insights into the molecular basis of endothelial activation/dysfunction in macro-and micro-vasculature of CoV-19 patients are provided.
Journal ArticleDOI
Regulation of cholesterol homeostasis in health and diseases: from mechanisms to targeted therapeutics
TL;DR: Based on the regulation of cholesterol homeostasis, many interventions have been developed to lower cholesterol by inhibiting cholesterol biosynthesis and uptake or enhancing cholesterol utilization and excretion as discussed by the authors . But, the benefits of those interventions for the treatment of multiple diseases including atherosclerotic cardiovascular diseases, obesity, diabetes, nonalcoholic fatty liver disease, cancer, neurodegenerative diseases, osteoporosis and virus infection.
Journal ArticleDOI
Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis
Hui Jiang,Yongwen Zhou,Seyed Mohammad Nabavi,Amirhossein Sahebkar,Peter J. Little,Suowen Xu,Jianping Weng,Jianjun Ge +7 more
TL;DR: This article provides a concise review of the formation of oxLDL, enzymes mediating LDL oxidation, and the receptors and pro-atherogenic signaling pathways ofOxLDL in vascular cells and explores how ox LDL functions in different stages of endothelial dysfunction and atherosclerosis.
References
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Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease
Paul M. Ridker,Brendan M. Everett,Tom Thuren,Jean G. MacFadyen,William Chang,Christie M. Ballantyne,Francisco H. Fonseca,Jose C. Nicolau,Wolfgang Koenig,Stefan D. Anker,John J.P. Kastelein,Jan H. Cornel,Prem Pais,Daniel Pella,Jacques Genest,Renata Cifkova,Alberto J. Lorenzatti,Tamás Forster,Zhanna Kobalava,Luminita Vida-Simiti,Marcus Flather,Hiroaki Shimokawa,Hisao Ogawa,Mikael Dellborg,Paulo Roberto Ferreira Rossi,Roland P.T. Troquay,Peter Libby,Robert J. Glynn +27 more
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