Endothelial Insulin Resistance of Freshly Isolated Arterial Endothelial Cells From Radial Sheaths in Patients With Suspected Coronary Artery Disease

Background-Endothelial insulin resistance is insulin-insensitivity in the vascular endothelium and can be observed in experimental models. This study aimed to investigate endothelial insulin resistance in patients with suspected coronary artery disease. To this end, a novel method of obtaining freshly isolated arterial endothelial cells from a radial catheter sheath was developed. Methods and Results-Freshly isolated arterial endothelial cells were retrieved from catheter sheaths placed in radial arteries for coronary angiography (n=69, patient age 64 - 12 years). The endothelial cells were divided into groups for incubation with or without insulin, vascular endothelial growth factor, or acetylcholine. The intensity of phosphorylated endothelial nitric oxide synthase at Ser1177 (p-eNOS) was quantified by immunofluorescence microscopy. The percentage increase of insulin-induced phosphorylated endothelial nitric oxide synthase correlated negatively with derivatives of reactive oxygen metabolites, an oxidative stress test (r=-0.348, n=53, P=0.011), E/E', an index of left ventricular diastolic dysfunction in Doppler echocardiography (rho=-0.374, n=49, P=0.008), and log-transformed brain natriuretic peptide (r=-0.266, n=62, P=0.037). Furthermore, percentage increase of insulin-induced p-eNOS was an independent factor for the cardio-ankle vascular index (standardized coefficient beta=-0.293, n=42, P=0.021) in the multivariate regression analysis of adaptive least absolute shrinkage and selection operator. Conclusions-Our results suggested that endothelial insulin resistance is associated with oxidative stress, left ventricular diastolic dysfunction, heart failure, and arterial stiffness.