Molecular Determinants of Functional Changes and Fibrosis Determined by Novel Automated Oscillometric Approach to Measure Brachial Artery Vascular Volume Elastic Modulus in Chronic Kidney Disease

Background: Simple arterial function measurements can be applied for atherosclerosis risk estimations. Recently, we developed a novel modality of an automated oscillometric method to measure brachial artery vascular elastic modulus (VE). We aimed to clarify whether VE reflected endothelial dysfunction related to chronic kidney disease (CKD) and to identify molecular determinants of VE in CKD. Methods: 12 CKD pts (eGFR 25.9±23.5 mL/min/1.73m2) and 15 controls were studied. Rest VE was measured by an automated oscillometric detector. VE was defined as [VE =ΔPressure/ (100XΔarea/Area) mmHg/%]. Using ultrasound, the brachial artery’s reactive hyperemia [flow mediated dilatation (FMD)] was measured. Endogenous inhibitors of nitric oxide synthase, symmetric dimethylarginine (SDMA), and arginine (Arg) were measured by HPLC. Galectin-3 (Gal-3), regulator of vascular fibrosis expressed in endothelium, was measured by ELISA. Results: CKD had lower FMD (4.86±3.37 vs 9.05±2.98 %, P=0.003) and higher VE than did controls (1.08±0.26 vs 0.83±0.17 mmHg/%, P=0.002). On multivariate analysis, decreased %FMD (P=0.0099), eGFR (P=0.0052), increased SDMA (P=0.0037), Arg (P=0.048), and Gal-3 (P=0.0022) were predictors for attenuated VE. Conclusions: Attenuated vascular elasticity detected by this approach correlated with reduced FMD in CKD. The molecular determinants of the attenuated VE were SDMA, Arg, and Gal-3. Thus, this simple measurement may reflect endothelial dysfunction and vascularACC2017 (American College of Cardiology 66th Annual Scientific Session

Comprehensive assessment of impaired coronary and peripheral artery vascular function in smokers using Oxygen-15 Labeled Water PET and Brachial Artery Ultrasound

Background: Cigarette smoking has impact on vascular function. Comprehensive evaluation of endothelial dependent (End) and endothelium independent (Endind) vascular function in coronary artery and peripheral artery in smokers has never been studied. The purpose of the present study was to evaluate the relationship between the coronary and peripheral vascular function in smokers using O-15 labeled water PET and brachial artery ultrasound.Methods: Eight active smokers (Brinkman index: 219.4±230.7) and 10 healthy individuals underwent brachial artery ultrasound at rest, reactive hyperemia [250 mmHg cuff occlusion (FMD)], and sublingual nitroglycerin (NTG) administration. Delta arterial diameter and %change of arterial diameter were calculated. Myocardial blood flow (MBF) was evaluated at rest, during adenosine triphosphate (ATP) administration, and cold pressor test (CPT) with O-15 water dynamic PET. Rest MBF and CPT MBF were corrected by rate pressure product (RPP).Results: Smokers significantly reduced End vasodilatation compared to control using ultrasound (delta FMD: 0.31±0.12 mm vs 0.44±0.11 mm, P=0.026, %FMD: 6.62±2.28% vs 11.29±2.75%, P=0.0014) and using O-15 water PET (RPP corrected CPT response: -18.0±10.1% vs 1.4±20.3%, P=0.04).There was no significant difference in NTG response (delta:0.73±0.30 mm vs 0.88±0.25 mm, P=0.27, %NTG: 15.9±6.8% vs 22.4±6.2%, P=0.055) and RPP corrected coronary flow reserve (3.19±1.22 vs 3.77±1.14, P=0.32) between the two groups. On the other hand, there was no relationship between coronary and peripheral End function (R=0.40, P=0.1) and Endind vascular function (R=0.24, P=0.3).Conclusions: Smokers exhibited impaired coronary endothelial function as well as peripheral endothelial function. In contrast, smokers did not show alteration in endothelial independent vasodilation . In addition, there was no correlation between PET and ultrasound measurements, possibly implying that while smokers may have systemic vascular endothelial dysfunction, the characteristics of that dysfunction may be different in coronary and peripheral arteries.ICNC 12, Nuclear Cardiology and Cardiac C

Accurate quantitative measurements of brachial artery cross-sectional vascular area and vascular volume elastic modulus using automated oscillometric measurements: comparison with brachial artery ultrasound.

Increasing vascular diameter and attenuated vascular elasticity may be reliable markers for atherosclerotic risk assessment. However, previous measurements have been complex, operator-dependent or invasive. Recently, we developed a new automated oscillometric method to measure a brachial artery\u27s estimated area (eA) and volume elastic modulus (VE). The aim of this study was to investigate the reliability of new automated oscillometric measurement of eA and VE. Rest eA and VE were measured using the recently developed automated detector with the oscillometric method. eA was estimated using pressure/volume curves and VE was defined as follows (VE=Δ pressure/ (100 × Δ area/area) mm Hg/%). Sixteen volunteers (age 35.2±13.1 years) underwent the oscillometric measurements and brachial ultrasound at rest and under nitroglycerin (NTG) administration. Oscillometric measurement was performed twice on different days. The rest eA correlated with ultrasound-measured brachial artery area (r=0.77, P<0.001). Rest eA and VE measurement showed good reproducibility (eA: intraclass correlation coefficient (ICC)=0.88, VE: ICC=0.78). Under NTG stress, eA was significantly increased (12.3±3.0 vs. 17.1±4.6 mm(2), P<0.001), and this was similar to the case with ultrasound evaluation (4.46±0.72 vs. 4.73±0.75 mm, P<0.001). VE was also decreased (0.81±0.16 vs. 0.65±0.11 mm Hg/%, P<0.001) after NTG. Cross-sectional vascular area calculated using this automated oscillometric measurement correlated with ultrasound measurement and showed good reproducibility. Therefore, this is a reliable approach and this modality may have practical application to automatically assess muscular artery diameter and elasticity in clinical or epidemiological settings.Hypertension Research advance online publication, 19 February 2015; doi:10.1038/hr.2015.6

Molecular Determinants of Functional and Fibrotic Changes by Novel Automated Oscillometric Approach to Measure Brachial Artery Vascular Volume Elastic Modulus.

Background: Simple arterial function measurements can be applied for atherosclerosis detections. We developed a novel modality involving an automated oscillometric method to measure brachial artery vascular elastic modulus (VE) possibly linked to endothelial function. We aimed to clarify whether VE reflected endothelial dysfunction related to chronic kidney disease (CKD) and to identify molecular determinants of VE and vascular stiffness in CKD. Methods: We included 12 CKD ptsand 15 controls. Rest VE was measured by an automated oscillometric detector. VE was defined as follows [VE =ΔPressure/ (100XΔarea/Area) mmHg/%]. The brachial artery’s reactive hyperemia [flow mediated dilatation (FMD)] was measured by ultrasound. Endogenous inhibitors of nitric oxide synthase, symmetric dimethylarginine (SDMA), and arginine (Arg) were measured by HPLC. Galectin-3 (Gal-3), regulator of vascular fibrosis expressed in endothelium, was measured by ELISA.Results: CKD showed lower FMD (P=0.003) and higher VE than controls (1.08±0.26 vs 0.83±0.17 mmHg/%, P=0.002). Multivariate analysis showed decreased %FMD, eGFR, increased SDMA, Arg, and Gal-3 were predictors for attenuated VE (P<0.05).Conclusions: Attenuated vascular elasticity detected by this oscillometric approach correlated with reduced FMD in CKD. The molecular determinants of the attenuated VE included SDMA, Arg, and Gal-3. Therefore, this simple oscillometric measurement may reflect endothelial dysfunction and vascular fibrosis.The 10th Congress of the Asian-Pacific Society on Thrombosis and Hemostasi

Vascular Elasticity Measured by Novel Brachial Artery Vascular Volume Elastic Modulus With Automated Oscillometry Reflects Molecular Determinant of Vascular Fibrosis

Background: Simple vascular functional measurements are desirable for atherosclerosis risk assessments. Recently, we developed a novel modality of automated oscillometric method to measure a brachial artery’s vascular elastic modulus (VE). Galectin-3 (Gal-3) expressed in endothelial cells regulates vascular fibrosis and is a molecular determinant of vascular stiffness. We aimed to clarify whether VE selectively correlates with marker of vascular stiffness in chronic kidney disease (CKD). Methods: 12 moderate-to-severe CKD (mean eGFR 25.9±23.5mL/min/1.73m2) and 15 controls were studied. Rest VE in brachial artery was measured by new automated oscillometric detector. VE was defined as follows [VE =ΔPressure/(100XΔarea/Area) mmHg/%]. Using ultrasound, the brachial artery’s reactive hyperemia [flow mediated dilatation (FMD)] was measured. Gal-3 and interleukin-6 were measured by enzyme-linked immunosorbent assay.Results: CKD had lower FMD (4.86±3.37 vs 9.05±2.98 %, P=0.003) and had attenuated VE than control (1.08±0.26 vs 0.83±0.17 mmHg/%, P=0.002). CKD had higher interleukin-6 (0.67±0.29 vs 0.29±0.33 pg/mL, P=0.003) and Gal-3 (20.0±12.4 vs. 5.84±2.83 pg/mL, P<0.001). VE was correlated negatively with %FMD (r=-0.46, P=0.015) and positively with Gal-3 (r=0.40, P=0.036) but not with interleukin-6 (r=0.21, P=0.28).Conclusions: Attenuated vascular elasticity detected by this novel approach closely correlated with increase in Gal-3 and reduced FMD in CKD. This may indicate that the attenuated vascular elasticity selectively reflects vascular fibrosis as evidenced by Gal-3 and subsequent endothelial responses to vascular stiffness.第80回日本循環器学会学術集

Vascular Elasticity Measured by Novel Brachial Artery Vascular Volume Elastic Modulus With Automated Oscillometry Correlates With Molecular Determinant of Vascular Fibrosis

Introduction: Simple vascular function measurements are desirable for atherosclerosis risk assessments. Recently, we developed a novel modality of automated oscillometric method to measure a brachial artery’s vascular elastic modulus (VE) and reported that VE is uninfluenced by blood pressure. Galectin-3 (Gal-3) expressed in endothelial cells regulates vascular fibrosis and is a molecular determinant of vascular stiffness. Hypothesis: We aimed to clarify whether VE selectively correlates with marker of vascular stiffness in chronic kidney disease (CKD). Methods: 12 moderate-to-severe CKD pts (mean eGFR 25.9±23.5 mL/min/1.73m2) and 15 controls were studied. Rest VE in brachial artery was measured by new automated oscillometric detector. VE was defined as follows [VE =ΔPressure/ (100XΔarea/Area) mmHg/%]. Using ultrasound, the brachial artery diameter at rest and during reactive hyperemia [flow mediated dilatation (FMD) with endothelial-dependent dilatation] was measured. Gal-3 and interleukin-6 (IL-6), a representative inflammatory marker, were measured by enzyme-linked immune assay.Results: CKD had lower FMD (4.86±3.37 vs 9.05±2.98 %, P=0.003) and had attenuated VE than control (1.08±0.26 vs 0.83±0.17 mmHg/%, P=0.002). CKD had higher IL-6 (0.67±0.29 vs 0.29±0.33 pg/mL, P=0.003) and higher Gal-3 (20.0±12.4 vs. 5.84±2.83 pg/mL, P<0.001). VE was negatively correlated with %FMD (r=-0.46, P=0.015) and correlated with Gal-3 (r=0.40, P=0.036) but not in IL-6 (r=0.21, P=0.28).Conclusions: Attenuated vascular elasticity detected by this novel approach closely correlated with increase in Gal-3 and reduced FMD in CKD. This may indicate that the attenuated vascular elasticity selectively reflects vascular fibrosis as evidenced by Gal-3 and subsequent endothelial responses to vascular stiffness. Thus, this oscillometric measurement may be useful for detecting vascular fibrosis information and dysfunction in endothelium level.American Heart Association scientific session 201