Assessment of Endothelial Function

Abstract

SummaryIn 1986, endothelial function was measured for the first time in patients with atherosclerotic coronary arteries. Since then, several methods for assessment of endothelial function, such as endothelium-dependent vasodilation induced by intra-arterial infusion of vasoactive agents using coronary angiography, Doppler flow guide wire, mercury-filled Silastic strain-gauge plethysmography, flow-mediated vasodilation, reactive hyperemia-peripheral arterial tonometry, and vascular response using an oscillometric method have been performed in humans. This review focuses on the assessment of endothelial function, including measurement history, methodological issues, and clinical perspectives. ( Results of studies on endothelial function in humans have shown reliable methods for measurement of endothelial function, relationships between atherosclerosis and endothelial function, mechanisms of endothelial dysfunction, and clinical implication such as the effects of interventions and cardiovascular events. Endothelial dysfunction is the initial step of atherosclerosis and is involved in the development of atherosclerosis, and it might increase the risk of cardiovascular and cerebrovascular diseases, resulting in cardiovascular events.1,2) It is possible that measurement of endothelial function will reveal one of the earliest changes that can be seen in atherosclerosis. Therefore, it is clinically important to assess endothelial function using an established method. Several methods have been used for assessment of endothelial function in humans, including endothelium-dependent vasodilation induced by intra-arterial infusion of vasoactive agents using coronary angiography, a Doppler flow guide wire, [3][4][5][6][7] and plethysmography, 8,9) as well as flow-mediated vasodilation (FMD), [10][11][12][13][14][15][16][17][18][19][20][21] reactive hyperemiaperipheral arterial tonometry (RH-PAT), 22,23) and vascular response using an oscillometric method. 24) Although vascular responses to intra-arterial infusion of vasoactive agents, such as agonists to stimulate nitric oxide (NO) release and antagonists of NO, should be considered as the gold standard for assessment of endothelial function, this technique is invasive and burdensome for the subjects. FMD elicited by shear stress-induced NO production from endothelial cells is now widely used worldwide. RH-PAT is also noninvasive, simple, and reproducible. Each method has advantages and disadvantages with respect to methodological aspects and clinical perspectives. Clinical Perspectives of Assessment of Endothelial FunctionStructure and physiology of the endothelium: Both vascular structure and function play an important role in the development and maintenance of atherosclerosis. If the endothelium of the whole body could be collected, its total weight would be equal to that of the liver, its total area would be equal to that of 6 tennis courts, and its total length is 100,000 km (2.5 times around the globe).2) Endothelial cells secrete various vasoactive agents such as vasodi...

An overview of AVF maturation and endothelial dysfunction in an advanced renal failure

“…Ultrasound flowmediated dilatation of the brachial artery is the most widely used in clinical research, and it is currently considered a standard for a non-invasive assessment of conduit artery endothelial function [35].…”

Assessment of endothelial function by flow-mediated dilation in diabetic patients: Effects of physical exercise

“…They demonstrated by the first time that the denuded endothelium (ECs were removed), caused lower relaxing response or even this response could be replaced by a vasoconstriction. They proposed that an endothelium-derived relaxing factor might be release from ECs in vascular tissue, later this factor was identified as nitric oxide (Higashi, 2015;Vanhoutte, Shimokawa, Feletou, & Tang, 2015). Surprisingly, ECs surface in an adult human, is composed of approximately 1 to 6 x 10 13 cells and its total length is enough to 2.5 times around the globe.…”

“…Therefore, the development of clinical tests for evaluating the normal or activated properties of endothelium is extremely useful in both clinical and basic research fields (Deanfield, Halcox, & Rabelink, 2007;Higashi, 2015). As a model of excellence, the tests should be safe, noninvasive, cheap, reproducible, and standardized between research groups.…”

“…It is expressed as a percentage change of the arterial diameter from the baseline diameter (Corretti et al, 2002;Harris, Nishiyama, Wray, & Richardson, 2010). FMD has been extensively used in clinical research and it is currently considered a standard for a noninvasive assessment of conduit artery endothelial function (Deanfield et al, 2007;Higashi, 2015). In addition, it was demonstrated a positive correlation between coronary response to acetylcholine and brachial vasodilator response to reactive hyperemia consolidating the use of this method (Anderson et al, 1995).…”

“…In addition, it has been pointed out that FMD percentage index can itself generates problems related to baseline diameter-dependency, which can led to biased comparisons of different conditions or populations. It should be emphasized that the researchers had to apply the allometric principles to scale FMD index and improve the interpretation of the protocol and results (Atkinson & Batterham, 2013, 2015Atkinson, 2014)albeit with small samples, that the scaling properties of FMD% can lead to biased inferences on endothelial dysfunction. Therefore, we aimed to investigate the underlying rationale and potential bias of FMD% using a selection of new examples from the large (n = 3499.…”