Endothelial Dysfunction: From Molecular Mechanisms to Measurement, Clinical Implications, and Therapeutic Opportunities

Health Faculty, UHI Millennium Institute, Inverness, University of Edinburgh, Edinburgh, Scotland.
Antioxidants & Redox Signaling (Impact Factor: 7.41). 10/2008; 10(9):1631-74. DOI: 10.1089/ars.2007.2013
Source: PubMed


Endothelial dysfunction has been implicated as a key factor in the development of a wide range of cardiovascular diseases, but its definition and mechanisms vary greatly between different disease processes. This review combines evidence from cell-culture experiments, in vitro and in vivo animal models, and clinical studies to identify the variety of mechanisms involved in endothelial dysfunction in its broadest sense. Several prominent disease states, including hypertension, heart failure, and atherosclerosis, are used to illustrate the different manifestations of endothelial dysfunction and to establish its clinical implications in the context of the range of mechanisms involved in its development. The size of the literature relating to this subject precludes a comprehensive survey; this review aims to cover the key elements of endothelial dysfunction in cardiovascular disease and to highlight the importance of the process across many different conditions.

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    • "It is believed that atherosclerotic changes in blood vessels in chronic renal diseases contribute significantly to the high cardiovascular morbidity and mortality. Morphological and functional abnormalities of the endothelium are considered as prodromal stage of atherosclerosis and early marker of CVD [6] that facilitate the progress of atherosclerosis [7] [8] and contribute to the development of hypertension through the enhancement of vascular resistance. On the other hand, arterial calcifications are a significant risk factor for cardiovascular mortality in the general population. "
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    ABSTRACT: Objective was to assess whether the concentration of malondialdehyde (MDA) as a marker of lipid peroxidation and serum concentration of matrix metalloproteinase-9 (MMP-9) are involved in the process of atherosclerosis in chronic kidney disease (CKD) patients nondialysis-dependent and those on peritoneal dialysis (PD), both with signs of cardiometabolic syndrome (CMS). Thirty CKD and 22 PD patients were included in a study. All observed patients were divided into three subgroups depending on the degree of atherosclerotic changes in the carotid arteries (CA). Severity of atherosclerotic changes in the CA was evaluated by ultrasonography. We confirmed significantly lower level of serum MDA throughout all the stages of atherosclerosis in PD patients compared with observed CKD patients (í µí±ƒ < 0.05) and increased serum concentration of MDA and MMP-9 with the progression of severity atherosclerotic changes in both groups of patients. The multiple regression analysis revealed that MDA and MMP-9 are significant predictors of changes in IMT-CA CKD patients (í µí±ƒ < 0.05) and plaque score on CA in these patients (í µí±ƒ < 0.05). The results suggest that MDA and MMP-9 could be mediators of CKD-related vascular remodeling in CMS.
    Mediators of Inflammation 10/2015; 2015(111). DOI:10.1155/2015/614357 · 3.24 Impact Factor
    • "Oxidative stress plays an important role in a wide range of diseases, including cancer [69], cardiovascular disease [70] and diabetes [71]. It is well known that low levels of ROS are involved in such insulin signal transduction, when present in low concentrations [7]. "
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    ABSTRACT: N-acetylcysteine (NAC), a cysteine pro-drug and glutathione precursor has been used in therapeutic practices for several decades, as a mucolytic agent and for the treatment of numerous disorders including paracetamol intoxication. There is a growing interest concerning the beneficial effects of NAC against the early stages of type-2 diabetes development. Nevertheless, the mechanisms underlying the therapeutic and clinical applications of NAC are not fully understood. In this review we aimed to focus on the protective effects of NAC against insulin resistance. The possible mechanisms of action were reviewed using the major findings of more than 100 papers relating the antioxidant, anti-inflammatory and anti-apoptotic properties of NAC. The anti-oxidative activity of NAC has been attributed to its fast reactions with free radicals as well as the restitution of reduced glutathione. Further, NAC has anti-inflammatory and anti-apoptotic properties which can have positive effects during the inflammatory process in insulin resistance. Moreover, NAC can modulate certain signaling pathways in both insulin target cells and β cells. The diverse biological effects of NAC may make it a potential adjuvant or therapeutic target in treatment of type-2 diabetes. So, further studies are required for determining its ability to alleviate insulin resistance and to improve insulin sensitivity. Copyright © 2015. Published by Elsevier Inc.
    Clinical biochemistry 04/2015; DOI:10.1016/j.clinbiochem.2015.04.017 · 2.28 Impact Factor
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    • "Functional diagnosis of endothelial dysfunction includes tests of endothelium dependent vasorelaxation, arterial stiffness and pulse wave propagation. Flow-mediated vasodilatation which uses high resolution ultrasound equipment to measure the post-occlusive increase in diameter and flow of brachial or radial arteries is reflective of the shear stress-stimulated production of nitric oxide (NO).[16] "
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    ABSTRACT: Migraine is a neurovascular disorder and any interventions improving endothelial function may contribute to its treatment and prevention of vascular complications like ischemic stroke. Yoga has been shown to have several beneficial effects on cardiovascular systems. However, no randomized controlled studies to date have investigated its effects on endothelial function of migraineurs. A total of 42 women patients with migraine were enrolled and randomized into either a Yoga exercise group or a control group. The control group received only medication for 12 weeks and the Yoga group was placed in yoga training program in addition to the same medical treatment. Blood test was given from all patients in order to measure plasma levels intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) after yoga training program. Totally 32 patients were participated in the final analyses (yoga: n = 18, control: n = 14). By analyzing data between yoga and control groups after the treatment period, there was a significant decreased in plasma level of VCAM in yoga group compare with the control group (15.29 ± 2.1 ng/ml vs. 21.70 ± 3.0 ng/ml, P < 0.05), whereas there was no significant difference in ICAM level between groups (19.1 ± 1.8 ng/ml vs. 20.97 ± 1.9 ng/ml P > 0.05). It seems that yoga exercises, as a complementary treatment beside pharmacological treatments, can be potentially an effective way of improving vascular functions in migraineurs.
    International journal of preventive medicine 04/2014; 5(4):424-9.
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