Role of Endothelial Dysfunction in Cardiovascular Disease: A Review

NADPH oxidases (NOX) are enzyme complexes that have received much attention as key molecules in the development of vascular dysfunction. NOX have the primary function of generating reactive oxygen species (ROS), and are considered the main source of ROS production in endothelial cells. The endothelium is a thin monolayer that lines the inner surface of blood vessels, acting as a secretory organ to maintain homeostasis of blood flow. The enzymatic production of nitric oxide (NO) by endothelial NO synthase (eNOS) is critical in mediating endothelial function, and oxidative stress can cause dysregulation of eNOS and endothelial dysfunction. Insulin is a stimulus for increases in blood flow and endothelium-dependent vasodilation. However, cardiovascular disease and type 2 diabetes are characterized by poor control of the endothelial cell redox environment, with a shift toward overproduction of ROS by NOX. Studies in models of type 2 diabetes demonstrate that aberrant NOX activation contributes to uncoupling of eNOS and endothelial dysfunction. It is well-established that endothelial dysfunction precedes the onset of cardiovascular disease, therefore NOX are important molecular links between type 2 diabetes and vascular complications. The aim of the current review is to describe the normal, healthy physiological mechanisms involved in endothelial function, and highlight the central role of NOX in mediating endothelial dysfunction when glucose homeostasis is impaired.

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Diabetes is a vascular disease: the role of endothelial dysfunction in pathophysiology of cardiovascular disease in diabetes

Cardiology Clinics ◽

10.1016/j.ccl.2004.07.001 ◽

2004 ◽

Vol 22 (4) ◽

pp. 505-509 ◽

Cited By ~ 16

Author(s):

Prakash C. Deedwania

Keyword(s):

Cardiovascular Disease ◽

Endothelial Dysfunction ◽

Vascular Disease

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Endothelial Dysfunction and Cardiovascular Disease: History and Analysis of the Clinical Utility of the Relationship

Biomedicines ◽

10.3390/biomedicines9060699 ◽

2021 ◽

Vol 9 (6) ◽

pp. 699

Author(s):

Peter J. Little ◽

Christopher D. Askew ◽

Suowen Xu ◽

Danielle Kamato

Keyword(s):

Cardiovascular Disease ◽

Endothelial Dysfunction ◽

Cell Monolayer ◽

Modern Times ◽

Protein Receptor ◽

Endocrine Secretion ◽

The Impact ◽

The Relationship ◽

Vascular Senescence

The endothelium is the single-cell monolayer that lines the entire vasculature. The endothelium has a barrier function to separate blood from organs and tissues but also has an increasingly appreciated role in anti-coagulation, vascular senescence, endocrine secretion, suppression of inflammation and beyond. In modern times, endothelial cells have been identified as the source of major endocrine and vaso-regulatory factors principally the dissolved lipophilic vosodilating gas, nitric oxide and the potent vascular constricting G protein receptor agonists, the peptide endothelin. The role of the endothelium can be conveniently conceptualized. Continued investigations of the mechanism of endothelial dysfunction will lead to novel therapies for cardiovascular disease. In this review, we discuss the impact of endothelial dysfunction on cardiovascular disease and assess the clinical relevance of endothelial dysfunction.

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Interactions between Epac1 and ezrin in the control of endothelial barrier function

Biochemical Society Transactions ◽

10.1042/bst20130271 ◽

2014 ◽

Vol 42 (2) ◽

pp. 274-278 ◽

Cited By ~ 9

Author(s):

Euan Parnell ◽

Stephen J. Yarwood

Keyword(s):

Cardiovascular Disease ◽

Endothelial Dysfunction ◽

Barrier Function ◽

Endothelial Barrier ◽

Endothelial Barrier Function ◽

Growing Body ◽

Cytoskeletal Dynamics ◽

Inflammatory Signalling ◽

Kinase A

Loss of barrier function in the vasculature promotes inflammatory signalling which in turn contributes to the progression of cardiovascular disease. cAMP can protect against endothelial dysfunction through the effectors PKA (protein kinase A) and Epac (exchange protein directly activated by cAMP). The present review outlines the role of Epac1 signalling within the endothelium and, in particular, the role of Epac1 in cytoskeletal dynamics and the control of cell morphology. The actin/cytoskeleton linker ezrin will be described in terms of the growing body of evidence placing it downstream of cAMP signalling as a mediator of altered cellular morphology.

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Pathophysiological Role of Adiponectin, Leptin and Asymmetric Dimethylarginine in the Process of Atherosclerosis

Folia Medica ◽

10.1515/folmed-2016-0039 ◽

2016 ◽

Vol 58 (4) ◽

pp. 234-240 ◽

Cited By ~ 8

Author(s):

Daniela Iv. Koleva ◽

Maria M. Orbetzova ◽

Julia G. Nikolova ◽

Tanya I. Deneva

Keyword(s):

Cardiovascular Disease ◽

Adipose Tissue ◽

Endothelial Dysfunction ◽

Proinflammatory Cytokines ◽

Asymmetric Dimethylarginine ◽

Serum Levels ◽

Reactive Protein ◽

Proinflammatory Mediators ◽

Pathophysiological Role

Abstract Adipose tissue is recognized as a rich source of proinflammatory mediators that may directly contribute to vascular injury, insulin resistance, and atherogenesis. Many studies have shown that adiponectin has antiatherogenic and anti-inflammatory properties. Adiponectin acts not only as a factor increasing insulin sensitivity, and the protective effect may result from its ability to suppress production of proinflammatory cytokines. It negatively regulates the expression of TNF-alpha and C-reactive protein (CRP) in adipose tissue; reduces expression of vascular and intracellular adhesion molecules (VCAM-1, ICAM-1), E-selectin, interleukin-8 (IL-8). Hyperleptinemia has been linked with the development of hypertension and endothelial dysfunction/atherosclerosis, two main pathophysiological conditions associated with cardiovascular disease development. Leptin-mediated increases in sympathetic nervous system activity may be among the principal mechanisms evoking obesity related hypertension. Leptin stimulates the secretion of proinflammatory cytokines, and increases the release of endothelin-1 (ET-1), which may promote hypertension. Increased serum levels of asymmetric dimethylarginine (ADMA), a physiological regulator of the biosynthesis of nitric oxide (NO), promote the process of atherosclerosis, leading to the occurrence of endothelial dysfunction and cardiovascular disease.

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