scholarly journals Endothelial function as a marker of pre-clinical atherosclerosis: assessment techniques and clinical implications

2015 ◽  
Vol 80 (3) ◽  
Author(s):  
Donatella Ruggiero ◽  
Stefania Paolillo ◽  
Giuseppe Della Ratta ◽  
Antonio Mariniello ◽  
Tiziana Formisano ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Ex Vivo ◽  
Clinical Indication ◽  
Diagnostic Tools ◽  
Special Focus ◽  
Peripheral Arteries ◽  
Doppler Flowmetry ◽  
Non Invasive

Endothelium plays a key role in maintenance of vascular homeostasis. Cardiovascular risk factors promote development of endothelial dysfunction, characterized by increased vasoconstriction and by procoagulant/pro-inflammatory endothelial activities. In coronary artery, endothelium-dependent dilation improves blood flow, while the occurrence of endothelial dysfunction reduces myocardial perfusion, so new methods have been developed for assessment of endothelial function in coronary and peripheral arteries. The quantitative angiography with intracoronary infusion of acetylcholine remains the “gold standard” to assess the endothelium-dependent vasodilatation. The use of this technique is restricted to patients who have a clinical indication for coronary angiography, so new imaging methods have been considered for noninvasive diagnosis of coronary microvascular disease, such as magnetic resonance imaging phase contrast and positron emission tomography. The advent of new techniques has facilitated testing of endothelial dysfunction in peripheral arteries with non-invasive methods. This review presents available invivo and ex-vivo methods for evaluating endothelial function with special focus on more recent ones. The diagnostic tools include local vasodilatation by venous occlusion plethysmography and assessment of flow-mediated dilatation, arterial pulse wave analysis and pulse amplitude tonometry, laser Doppler flowmetry. The possibility to detect endothelial dysfunction as an early marker of atherosclerosis makes these instruments useful for early stratification of patients at risk for cardiovascular events. Aim of this review is to summarize the characteristics of non-invasive assessment of endothelial function in order to optimize cardiovascular risk management.

scholarly journals Methods for evaluating endothelial function: a position statement from the European Society of Cardiology Working Group on Peripheral Circulation

2011 ◽  
Vol 18 (6) ◽  
pp. 775-789 ◽  
Author(s):  
John Lekakis ◽  
Pierre Abraham ◽  
Alberto Balbarini ◽  
Andrew Blann ◽  
Chantal M Boulanger ◽  
...  
Keyword(s):  
Endothelial Function ◽  
Cardiovascular Health ◽  
Ex Vivo ◽  
Pulse Amplitude ◽  
Peripheral Circulation ◽  
Microvascular Blood Flow ◽  
Disease Assessment ◽  
Special Focus ◽  
Doppler Flowmetry

The endothelium holds a pivotal role in cardiovascular health and disease. Assessment of its function was until recently limited to experimental designs due to its location. The advent of novel techniques has facilitated testing on a more detailed basis, with focus on distinct pathways. This review presents available in-vivo and ex-vivo methods for evaluating endothelial function with special focus on more recent ones. The diagnostic modalities covered include assessment of epicardial and microvascular coronary endothelial function, local vasodilation by venous occlusion plethysmography and flow-mediated dilatation, arterial pulse wave analysis and pulse amplitude tonometry, microvascular blood flow by laser Doppler flowmetry, biochemical markers and bioassays, measurement of endothelial-derived microparticles and progenitor cells, and glycocalyx measurements. Insights and practical information on the theoretical basis, methodological aspects, and clinical application in various disease states are discussed. The ability of these methods to detect endothelial dysfunction before overt cardiovascular disease manifests make them attractive clinical tools for prevention and rehabilitation.

scholarly journals Endothelial dysfunction in hypertension: pathophysiological mechanism or marker of cardiovascular risk?

2013 ◽  
pp. 82-86
Author(s):  
Lorenzo Ghiadoni ◽  
Agostino Virdis ◽  
Francesco Stea ◽  
Rosa M. Bruno ◽  
Stefano Taddei
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Peripheral Circulation ◽  
Vascular Damage ◽  
Pathophysiological Mechanism ◽  
Cardiovascular Research ◽  
Non Invasive

Introduction Vascular endothelial production of nitric oxide (NO) plays an important role in the modulation of vessel tone and structure, protecting the vascular wall from atherosclerosis. In pathological conditions, however, the endothelium also produces pro-atherogenic substances (mainly reactive oxygen species), which inactivate NO. The Endothelial dysfunction, induced by reduced NO availability, is known to contribute to the development and progression of vascular damage. For this reason, endothelial function has been a major focus of cardiovascular research in the last few decades. Because NO has a very short half-life and its in vivo measurement is difficult, many researchers prefer to measure its biological activity, particularly the NO-dependent vasodilation, at the level of the coronary and peripheral circulation by endothelial stimuli. The most widely used technique involves measurement of brachial artery flow-mediated dilation. This test allows non-invasive evaluation of endothelium-dependent vasodilation in the peripheral macrocirculation induced by a mechanical stimulus (increase in shear stress caused by 5 minutes of forearm ischemia). The vasodilatatory response is reduced in the presence of major cardiovascular risk factors, particularly essential hypertension. Conclusions Studies conducted mainly in high-risk patients have demonstrated that endothelial dysfunction within the coronary or peripheral circulation is predictive of cardiovascular events (independently of classical risk factors). Drug therapy can improve endothelial function by increasing the availability of NO (a possible adjunctive benefit in terms of preventing vascular damage and improving the prognosis). Future studies will establish whether the evaluation of endothelial function by non-invasive, standardized, reproducible, low-cost techniques is an important test for cardiovascular risk stratification in clinical practice.

scholarly journals Fast Optoacoustic Mesoscopy of Microvascular Endothelial Dysfunction in Cardiovascular Risk and Disease

2021 ◽  
Author(s):  
Hailong He ◽  
Angelos Karlas ◽  
Nikolina-Alexia Fasoula ◽  
Michael Kallmayer ◽  
Juan Aguirre ◽  
...  
Keyword(s):  
Cardiovascular Risk ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vessel Diameter ◽  
Skin Depth ◽  
Total Blood ◽  
Doppler Flowmetry ◽  
Early Marker ◽  
Microvascular Endothelial

Microvascular endothelial dysfunction (ED) precedes the ED in larger arteries and is an early marker of cardiovascular disease (CVD). While precise assessment of microvascular ED could thus be used for the early detection and risk stratification of CVD, detailed interrogation of skin microvascular ED is limited by the technology available. Herein, we applied a novel approach for the non-invasive assessment of skin microvascular ED by developing fast plane raster-scan optoacoustic mesoscopy (FP-RSOM) to visualize and quantify skin microvasculature perfusion changes during post-occlusive hyperemia (PORH) tests. We combined static three-dimensional RSOM imaging with fast dynamic FP-RSOM measurements (1 frame / second) in human skin in vivo, which allowed for the first time to fully visualize the cutaneous microvascular response and further quantify changes of individual vessel diameter, total blood volume and vessel density during the PORH process. We further computed biomarkers from FP-RSOM images to quantify skin endothelial function within different skin layers as a function of skin depth, while conventional approaches mainly measure overall changes within sampled tissue volumes. FP-RSOM applied on smokers and patients with CVD showed clear ED in both groups compared to healthy volunteers. Moreover, FP-RSOM imaging showed higher sensitivity in quantifying the effects of smoking and CVD on skin microvascular endothelial function compared to clinically used laser Doppler flowmetry and tissue spectrometry (O2C). Our study introduces FP-RSOM as a novel tool to visualize and quantify skin microvascular ED as an early marker for the diagnostics and monitoring of cardiovascular risk and disease.

scholarly journals A pilot study to establish non-invasive biomarkers for higher-grade meningioma

2019 ◽  
Vol 21 (Supplement_4) ◽  
pp. iv6-iv6
Author(s):  
Daniele Baiz ◽  
Caterina Negroni ◽  
Emanuela Ercolano ◽  
Claire L Adams ◽  
Kathreena M Kurian ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Tumour Progression ◽  
Primary Tumour ◽  
Regulation Of Gene Expression ◽  
Diagnostic Tools ◽  
Malignant Tumours ◽  
Liquid Biopsies ◽  
Benign Meningioma ◽  
Non Invasive ◽  
Serum Exosomes

Abstract Introduction Meningioma brain tumours are the most common primary tumour in adults. Despite surgery and/or radiation therapy, meningioma may recur. The 5-year recurrence rate in benign meningioma is estimated in about 10% while much greater in atypical and malignant tumours. MicroRNAs (miRNAs) represent a large class of small RNAs driving regulation of gene expression and playing a role in tumour progression and therefore proposed as diagnostic tools. Moreover, miRNAs can be released from tumour cells into the blood stream via exosomes, showing potential to be used as liquid biopsies. Methods Identification of novel circulating biomarkers was conducted by performing an unbiased Cancer MicroRNA qPCR Array, followed by bioinformatics analysis. In parallel, we conducted a biased in silico analysis of the miRNAs targeting Cyclin D1 and E1, recently proposed as immunohistochemical meningioma biomarkers. Validation studies performed using TaqMan® reagents. Results Stringent unbiased (p<0.01) miRNA profiling followed by validation in ex vivo samples revealed that the miR-9-1 is upregulated in higher-grade meningioma tissues and serum exosomes, controlled by the EGFR/AP-1 axis and correlated with lower levels of E-Cadherin, a proposed biomarker for malignant meningioma. On the contrary, biased analysis, followed by validation in vitro and ex vivo, showed that the miR-497~195 cluster is downregulated in higher-grade meningioma tissues and serum exosomes, correlating with the overexpression of GATA-4, a novel meningioma tissue biomarker. Conclusion Our data demonstrated that both miR-497~195 and miR-9-1 show potential to become promising non-invasive biomarkers for higher-grade meningioma, reflecting their expression status in tissues. (DB and CN contributed equally).

Differential effects of obesity on visceral vs. subcutaneous adipose arteries: role of shear activated Kir2.1 and alterations to the glycocalyx

2021 ◽  
Author(s):  
Sang Joon Ahn ◽  
Elizabeth Le Master ◽  
James C. Lee ◽  
Shane A. Phillips ◽  
Irena Levitan ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Ex Vivo ◽  
Flow Chamber ◽  
Dominant Negative ◽  
Obese Mice ◽  
Shear Sensitivity ◽  
Electrophysiological Recordings ◽  
Subcutaneous Adipose

Obesity imposes well-established deficits to endothelial function. We recently showed that obesity-induced endothelial dysfunction was mediated by disruption of the glycocalyx and a loss of Kir channel flow-sensitivity. However, obesity-induced endothelial dysfunction is not observed in all vascular beds: visceral adipose arteries (VAA), but not subcutaneous adipose arteries (SAA), exhibit endothelial dysfunction. Aim: To determine if differences in SAA vs. VAA endothelial function observed in obesity are attributed to differential impairment of Kir channels and alterations to the glycocalyx. Methods: Mice were fed a normal rodent diet, or a high fat Western diet to induce obesity. Flow-induced vasodilation (FIV) was measured ex vivo. Functional downregulation of endothelial Kir2.1 was accomplished by transducing adipose arteries from mice and obese humans with adenovirus containing a dominant-negative Kir2.1 construct. Kir function was tested in freshly isolated endothelial cells seeded in a flow chamber for electrophysiological recordings under fluid shear. Atomic force microscopy was used to assess biophysical properties of the glycocalyx. Results: Endothelial dysfunction was observed in VAA of obese mice and humans. Downregulating Kir2.1 blunted FIV in SAA, but had no effect on VAA, from obese mice and humans. Obesity abolished Kir shear-sensitivity in VAA endothelial cells and significantly altered the VAA glycocalyx. In contrast, Kir shear-sensitivity was observed in SAA endothelial cells from obese mice and effects on SAA glycocalyx were less pronounced. Conclusions: We reveal distinct differences in Kir function and alterations to the glycocalyx that we propose contribute to the dichotomy in SAA vs. VAA endothelial function with obesity.

Abstract 13062: Epicardial Fat Associates With Endothelial Dysfunction, but Not With Coronary Calcium Score: From the Elsa-brasil Cohort Study

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Karina P Martins ◽  
Sandhi Barreto ◽  
Daniel Bos ◽  
JESIANA PEDROSA ◽  
Douglas Mesquita ◽  
...  
Keyword(s):  
Risk Factors ◽  
Cardiovascular Risk ◽  
Coronary Artery ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Cardiovascular Risk Factors ◽  
Subcutaneous Fat ◽  
Epicardial Fat ◽  
Fat Deposits ◽  
Multivariable Analyses

Introduction: Epicardial fat has been related to coronary artery disease (CAD) independent of visceral or subcutaneous fat. The mechanism responsible for this association has not yet been elucidated. Our objective was to evaluate the association between automatically measured epicardial fat volume (EFV), cardiovascular risk factors, coronary artery calcium (CAC) and endothelial function in participants of ELSA-Brasil. Methods and Results: The sample comprised 470 (mean age 55± 8y, 52.3% men) participants from ELSA-MG, one of the Investigation Centers of the cohort, who had valid computed tomography scans and endothelial function evaluated by peripheral arterial tonometry (PAT). The mean EFV was 111 (IQ 86-144) mL. CAC=0 was detected in 55% of participants. In the multivariable analyses between cardiovascular risk factors and EFV, the following associations were observed with higher EFV: female sex; and increased age, waist circumference and triglycerides (p <0.001 for all). In multivariable analyses, higher EFV remained associated with worse endothelial function - basal pulse amplitude (q2=1.22, CI95% 1.07-1.40, p=0.004; q3=1.50, CI95% 1.30-1.74, p<0.001; q4=1.50, CI95% 1.28-1.79, p<0.001) and PAT ratio (q2=0.87, CI95% 0.81-0.95, p<0.001; q3=0.86, CI95% 0.79-0.94, p<0.001; q4=0.80, CI95% 0.73-0.89, p<0.001), but not with CAC. Conclusions: Higher EFV was associated with impaired endothelial function, but not with higher CAC. Our results suggest that the mechanism by which epicardial fat deposits relates to CAD may be different from the pathway of CAC, which relates to calcified plaques. A possible mechanism may be through the enhancement of endothelial dysfunction, microvascular disease and predominantly lipidic non-calcified plaques.

Abnormal endothelial vasomotor and secretory function

2015 ◽  
Author(s):  
Thimoteus Speer ◽  
Danilo Fliser
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Inflammation ◽  
Secretory Function ◽  
Vascular Integrity ◽  
Non Invasive ◽  
Other Substances ◽  
Modified Lipoproteins ◽  
And Function

The endothelium plays a crucial role in the maintenance of vascular integrity and function. Nitric oxide produced by endothelial cells is a key player, inducing relaxation of vascular smooth muscle cells, inhibition of vascular inflammation, and prevention of coagulatory activation. Chronic kidney disease (CKD) is characterized by deterioration of different protective endothelial properties, collectively described as endothelial dysfunction. Several factors such as methylarginines, modified lipoproteins, and other substances that accumulate may be involved in the pathogenesis of endothelial dysfunction of CKD. Endothelial dysfunction is suggested to be the first critical step in the initiation of atherosclerosis. Clinical assessment of endothelial function may become important in recognition of patients with increased cardiovascular risk. Beside several invasive and non-invasive methods to assess endothelial function in vivo, measurement of circulating (bio)markers may be useful for the evaluation of endothelial dysfunction.

scholarly journals Endothelial Dysfunction as a Link Between Cardiovascular Risk Factors and Peripheral Neuropathy in Diabetes

2016 ◽  
Vol 101 (9) ◽  
pp. 3401-3408 ◽  
Author(s):  
Matthieu Roustit ◽  
Jordan Loader ◽  
Carly Deusenbery ◽  
Dimitrios Baltzis ◽  
Aristidis Veves
Keyword(s):  
Risk Factors ◽  
Cell Adhesion ◽  
Cardiovascular Risk ◽  
Peripheral Neuropathy ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Cardiovascular Risk Factors ◽  
Medical Center ◽  
Glycosylated Hemoglobin ◽  
Disability Score

Abstract Context: Cardiovascular risk factors are well-known predictors of the development of diabetic peripheral neuropathy (DPN), which has traditionally been considered as a manifestation of diabetes-associated microangiopathy. Because endothelial dysfunction is strongly associated with all cardiovascular risk factors, we hypothesized that it may be a link between cardiovascular risk factors and DPN. Objective: The primary objective of this study was to test whether endothelial dysfunction is a predictor of DPN. Design and Setting: This is a cross-sectional analysis of a cohort composed of patients followed at the Microcirculatory Laboratory, Beth Israel Deaconess Medical Center. Patients: Participants with diabetes without DPN (n = 192) and with DPN (n = 166), subjects with prediabetes (n = 75), and nondiabetic controls (n = 59) were included. Interventions: Endothelial function was assessed with flow-mediated dilation (FMD) of the brachial artery. Inflammatory cytokines and biomarkers of endothelial function (soluble intercellular and vascular cell adhesion molecules) were quantified using a multiplex bead-based immunoassay. Neurological assessment included the neuropathy disability score (NDS). Main Outcome Measure: The relationship between FMD and NDS assessed using multiple linear regression. Results: In addition to already known risk factors of DPN, FMD was strongly associated with NDS (β = −0.24; P &lt; .001). Sensitivity analysis that removed FMD from the model provided similar results for soluble intercellular cell adhesion molecule-1, another biomarker of endothelial function. Confirmatory factor analysis further showed that endothelial dysfunction is a significant mediator between glycosylated hemoglobin and diabetes duration and diabetic complications. Conclusions: This study shows that endothelial dysfunction occurs early in the pathophysiology of diabetes and is a link between cardiovascular risk factors and DPN.

Endothelial dysfunction by acute hyperhomocyst(e)inaemia: restoration by folic acid

1999 ◽  
Vol 96 (3) ◽  
pp. 235-239 ◽  
Author(s):  
Michiaki USUI ◽  
Hidehiro MATSUOKA ◽  
Hiroshi MIYAZAKI ◽  
Seiji UEDA ◽  
Seiya OKUDA ◽  
...  
Keyword(s):  
Body Weight ◽  
Risk Factor ◽  
Folic Acid ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Plasma Levels ◽  
Folic Acid Supplementation ◽  
Non Invasive ◽  
Per Se ◽  
High Resolution Ultrasonography

Recent evidence demonstrates that hyperhomocyst(e)inaemia is a novel risk factor for cardiovascular diseases. In patients with chronic hyperhomocyst(e)inaemia, endothelial function is impaired. However, whether hyperhomocyst(e)inaemia per se is a cause or an epiphenomenon of endothelial dysfunction remains unknown. In this study, we examined the effects of methionine-induced acute hyperhomocyst(e)inaemia on human endothelial function. In healthy volunteers we administered methionine (0.1 ;g/kg body weight, per os), a substrate of homocyst(e)ine, with or without folic acid (20 ;mg, per os) and examined flow-mediated vasodilatation of the brachial artery by high-resolution ultrasonography as a non-invasive measure of endothelial function. We also measured plasma levels of homocyst(e)ine before and 3, 8 and 24 ;h after methionine loading. Methionine administration increased plasma levels of homocyst(e)ine by four times the basal level at 8 ;h (P< 0.0001, ANOVA). The plasma levels returned to baseline at 24 ;h. Flow-mediated vasodilatation was significantly decreased to half of the baseline value at 8 ;h and returned to baseline at 24 ;h (P< 0.0001, ANOVA), whereas endothelium-independent vasodilatation by glyceryl trinitrate was not affected by the methionine loading. Co-administration of folic acid did not attenuate methionine-induced hyperhomocyst(e)inaemia but completely prevented endothelial dysfunction. Our results suggest that in humans a methionine-rich diet may acutely impair endothelial function, which can be prevented by folic acid supplementation.

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