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 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 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 Comparison of biomarkers of endothelial dysfunction and microvascular endothelial function in patients with primary aldosteronism and essential hypertension

2021 ◽  
Vol 22 (1) ◽  
pp. 147032032199949
Author(s):  
Miaomiao Sang ◽  
Yu Fu ◽  
Chenmin Wei ◽  
Jing Yang ◽  
Xueting Qiu ◽  
...  
Keyword(s):  
Essential Hypertension ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Primary Aldosteronism ◽  
Cardiovascular Events ◽  
Statistical Significance ◽  
Enzyme Linked Immunosorbent Assay ◽  
Microvascular Endothelial ◽  
Pai 1 ◽  
Microvascular Endothelial Function

Introduction: Studies have shown that primary aldosteronism (PA) has a higher risk of cardiovascular events than essential hypertension (EH). Endothelial dysfunction is an independent predictor of cardiovascular events. Whether PA and EH differ in the endothelial dysfunction is uncertain. Our study was designed to investigate the levels of biomarkers of endothelial dysfunction (Asymmetric dimethylarginine, ADMA; E-selectin, and Plasminogen activator inhibitor-1, PAI-1) and assess the microvascular endothelial function in patients with PA and EH, respectively. Methods: The biomarkers of endothelial dysfunction were measured by enzyme-linked immunosorbent assay (ELISA). Microvascular endothelial function was evaluated by Pulse amplitude tonometry (PAT). Results: Thirty-one subjects with EH and 36 subjects with PA including 22 with aldosterone-producing adenoma (APA) and 14 with idiopathic hyperaldosteronism (IHA) were enrolled in our study. The ADMA levels among the three groups were different (APA 47.83 (27.50, 87.74) ng/ml vs EH 25.08 (22.44, 39.79) ng/ml vs IHA 26.00 (22.23, 33.75) ng/ml; p = 0.04), however, when the APA group was compared with EH and IHA group, there was no statistical significance (47.83 (27.50, 87.74) ng/ml vs 25.08 (22.44, 39.79) ng/ml for EH, p = 0.11; 47.83 (27.50, 87.74) ng/ml vs IHA 26.00 (33.75) ng/ml, p = 0.07). The results of ADMA levels are presented as Median (p25, p75). Whereas, levels of PAI-1 and E-selectin, microvascular endothelial function were not significantly different between PA and EH subjects. Conclusions: Our study shows no significant differences between PA and EH in terms of biomarkers of endothelial dysfunction and microvascular endothelial function. The microvascular endothelial function of PA and EH patients is comparable.

scholarly journals Circulating biologic markers of endothelial dysfunction in cerebral small vessel disease: A review

2015 ◽  
Vol 36 (1) ◽  
pp. 72-94 ◽  
Author(s):  
Anna Poggesi ◽  
Marco Pasi ◽  
Francesca Pescini ◽  
Leonardo Pantoni ◽  
Domenico Inzitari
Keyword(s):  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Small Vessel Disease ◽  
Brain Magnetic Resonance Imaging ◽  
Cerebral Small Vessel Disease ◽  
Small Vessel ◽  
Perivascular Spaces ◽  
Vessel Disease ◽  
Brain Changes

The term cerebral small vessel disease (SVD) refers to a group of pathologic processes with various etiologies that affect small arteries, arterioles, venules, and capillaries of the brain. Magnetic resonance imaging (MRI) correlates of SVD are lacunes, recent small subcortical infarcts, white-matter hyperintensities, enlarged perivascular spaces, microbleeds, and brain atrophy. Endothelial dysfunction is thought to have a role in the mechanisms leading to SVD-related brain changes, and the study of endothelial dysfunction has been proposed as an important step for a better comprehension of cerebral SVD. Among available methods to assess endothelial function in vivo, measurement of molecules of endothelial origin in peripheral blood is currently receiving selective attention. These molecules include products of endothelial cells that change when the endothelium is activated, as well as molecules that reflect endothelial damage and repair. This review examines the main molecular factors involved in both endothelial function and dysfunction, and the evidence linking endothelial dysfunction with cerebral SVD, and gives an overview of clinical studies that have investigated the possible association between endothelial circulating biomarkers and SVD-related brain changes.

scholarly journals Arginase inhibition restores NOS coupling and reverses endothelial dysfunction and vascular stiffness in old rats

2009 ◽  
Vol 107 (4) ◽  
pp. 1249-1257 ◽  
Author(s):  
Jae Hyung Kim ◽  
Lukasz J. Bugaj ◽  
Young Jun Oh ◽  
Trinity J. Bivalacqua ◽  
Sungwoo Ryoo ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Vascular Stiffness ◽  
Arginase Activity ◽  
Young Rats ◽  
Arginase 1 ◽  
Enos Uncoupling ◽  
Old Rats

There is increasing evidence that upregulation of arginase contributes to impaired endothelial function in aging. In this study, we demonstrate that arginase upregulation leads to endothelial nitric oxide synthase (eNOS) uncoupling and that in vivo chronic inhibition of arginase restores nitroso-redox balance, improves endothelial function, and increases vascular compliance in old rats. Arginase activity in old rats was significantly increased compared with that shown in young rats. Old rats had significantly lower nitric oxide (NO) and higher superoxide (O2−) production than young. Acute inhibition of both NOS, with NG-nitro-l-arginine methyl ester, and arginase, with 2( S)-amino- 6-boronohexanoic acid (ABH), significantly reduced O2− production in old rats but not in young. In addition, the ratio of eNOS dimer to monomer in old rats was significantly decreased compared with that shown in young rats. These results suggest that eNOS was uncoupled in old rats. Although the expression of arginase 1 and eNOS was similar in young and old rats, inducible NOS (iNOS) was significantly upregulated. Furthermore, S-nitrosylation of arginase 1 was significantly elevated in old rats. These findings support our previously published finding that iNOS nitrosylates and activates arginase 1 (Santhanam et al., Circ Res 101: 692–702, 2007). Chronic arginase inhibition in old rats preserved eNOS dimer-to-monomer ratio and significantly reduced O2− production and enhanced endothelial-dependent vasorelaxation to ACh. In addition, ABH significantly reduced vascular stiffness in old rats. These data indicate that iNOS-dependent S-nitrosylation of arginase 1 and the increase in arginase activity lead to eNOS uncoupling, contributing to the nitroso-redox imbalance, endothelial dysfunction, and vascular stiffness observed in vascular aging. We suggest that arginase is a viable target for therapy in age-dependent vascular stiffness.

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.

Abstract 1421: In Vivo Measurement of Flow-Mediated Vasodilation in Living Rats using High Resolution Ultrasound: Age-Dependent Endothelial Dysfunction

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Christian Heiss ◽  
Richard E Sievers ◽  
Nicolas Amabile ◽  
Tony Y Momma ◽  
Shobha Natarajan ◽  
...  
Keyword(s):  
High Resolution ◽  
Endothelial Dysfunction ◽  
Endothelial Function ◽  
Femoral Artery ◽  
Reactive Hyperemia ◽  
Surrogate Marker ◽  
Flow Measurements ◽  
Age Related ◽  
Age Dependent

In humans, endothelial function serves as a surrogate marker for cardiovascular health and is measured as changes in arterial diameter after temporary ischemia (flow-mediated dilation; FMD). We developed an FMD-related approach to study conduit artery vasodilation in living rats, and demonstrate a reduction in FMD in older versus younger animals consistent with age-related endothelial dysfunction. Diameter and Doppler-flow measurements were obtained from the femoral artery using high-resolution ultrasound (35 MHz). We observed dose-dependent vasodilation using both endothelium-dependent and endothelium-independent pharmacologic vasodilators (acetylcholine and nitroglycerine). Flow-dependent vasodilation was observed in response to flow increase induced both by adenosine and local saline infusion. Transient hindlimb ischemia led to reactive hyperemia with sequential flow velocity increase and femoral artery dilation, the latter of which was completely abolished by NO-synthase (NOS) inhibition with L-NMMA. To demonstrate its applicability in a model of endothelial dysfunction, we show that FMD is significantly reduced in older versus younger animals. While FMD was completely NOS-dependent in younger animals, NOS-dependent mechanisms accounted for only half of the FMD in older animals, with the remainder being blocked by charybdotoxin (CTx) and apamin suggesting contribution of endothelium-derived-hyperpolarizing-factor. Using this new integrative physiologic model to reproducibly study FMD in living rats, we show that age-dependent endothelial dysfunction is accompanied by a shift in mechanisms underlying vasodilatory endothelial function.

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.

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