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
