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 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

Novel Arterial Vascular Volume Elastic Modulus with Automated Oscillometric Approach Accurately Detected Endothelial and Endothelial Independent Vascular Function in CKD

Background: Simple and automated vascular function measurements are desirable for atherosclerosis risk assessments. Vascular elastic modulus (VE) is uninfluenced by blood pressure and is potentially linked to vascular function. Recently, we developed a novel modality of automated oscillometric method to measure a brachial artery´s VE and estimated arterial cross sectional area (eA). We aimed to investigate whether VE and eA response to nitroglycerin (NTG) reflected endothelial and endothelial independent dysfunction related to chronic kidney disease (CKD). Methods: 13 moderate-to-severe CKD (mean estimated glomerular filtration rate [eGFR]: 29.3±25.7 mL/min/1.73m2) and 15 controls were studied. Rest VE and eA response to NTG were measured by novel automated oscillometric detector. eA was estimated using pressure-volume curves and VE was defined as follows [VE=ΔPressure/ (100XΔarea/Area) mmHg/%]. Ultrasound measurements of flow mediated vasodilatation (FMD) and NTG were used as standard.Results: CKD had lower FMD than control (4.97±3.24 vs 9.03±2.98 %, P=0.002) and attenuated VE (1.09±0.25 vs 0.83±0.17 mmHg/%, P=0.003). Rest Ve was negatively correlated with %FMD(r=-0.43, P=0.02). Percent eA increase after NTG was correlated with %vascular diameter increase with ultrasound(r=0.51, P=0.005). However, there was no difference in %NTG(P=0.16) with ultrasound or %eA change (P=0.34) between the two groups.Conclusions: This new automated vascular function measurement using oscillometric measurement reliably detected endothelial dysfunction related to CKD and has potential to detect endothelial independent vasodilator response.第79回日本循環器学会学術集