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

ABSTRACT: 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 (?=-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 ?=-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.

SUBMITTER: Masaki N

PROVIDER: S-EPMC6475050 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Masaki Nobuyuki N Ido Yasuo Y Yamada Toshiyuki T Yamashita Youhei Y Toya Takumi T Takase Bonpei B Hamburg Naomi M NM Adachi Takeshi T

Journal of the American Heart Association 20190301 6

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 radia ...[more]

PMID: 30885039

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Project description:Background:Studies have demonstrated that female sex is an adverse risk factor in CABG. The primary aim of this study was to determine whether the radial artery (RA) was associated with reduced angiographic occlusion compared to the saphenous vein graft (SVG) stratified by sex in the multi-centered Radial Artery Patency Study (NCT00187356). Methods:Between 1996-2001, 529 patients less than 80 years, with graftable triple-vessel disease underwent isolated CABG across 11 centers with late angiographic and clinical follow-up. The primary objective was to compare complete occlusion of RA and SVG with respect to sex. The secondary objective was to determine cumulative patency of both grafts along with predictors of late graft occlusion stratified by sex. The additional objective was to compare major adverse cardiac events (MACE, defined as cardiac mortality, myocardial infarction or re-intervention) between women and men. Results:Of the 529 enrolled patients (13.4% women), 269 (women: n=41, 15.2%) underwent late angiography at a mean of 7.7±1.5 years after CABG. Women were older (64.1±6.7 versus 59.1±8.0 years, P<0.01) with a higher rate of diabetes (43.9% versus 28.5%, P=0.05). Smoking history was less common (48.8% versus 75.4%, P<0.01) while the mean number of grafts per patient were similar (women: 3.8±0.7, men: 3.8±0.6, P=0.65). RA occlusions were lower than SVG in women (RA: 9.8%, SVG: 26.8%, P=0.05) and in men (RA: 8.8%, SVG: 17.1%, P=0.01). The rate of RA and SVG occlusion was not statistically different between women and men, and cumulative patency curves were also similar between sexes for the RA and study SVG. Multivariable modeling showed that having a RA (versus SVG) was protective in women [odds ratio (OR) 0.15, P=0.04] and men: (OR 0.49, P=0.02). MACE (P=0.15) and event-free cardiac survival (log-rank P=0.14) were similar between women and men. Conclusions:Radial arteries are protective in both women and men with comparable burden of coronary disease and revascularization.

Project description:BackgroundLipoprotein-associated Phospholipase A2 (Lp-PLA2), can exert proinflammatory as well as proatherogenic properties on the vascular wall. The current study sought to evaluate the influence of high Lp-PLA2 levels on indices of arterial wall properties in patients with stable coronary artery disease (CAD).MethodsThree hundred seventy-four consecutive patients with stable CAD (mean age 61 ± 11 years, 89% males) were enrolled in this single-center cross-sectional study. Flow-mediated dilation (FMD) was used to assess endothelial function and augmentation index (AIx) of the central aortic pressure was used to assess reflected waves. ELISA was used to determine Lp-PLA2 serum levels.ResultsAfter dividing the participants in 3 equal groups based on the tertiles of circulating Lp-PLA2 values, no significant differences were demonstrated between those in the 3rd tertile with Lp-PLA2 values > 138 μg/L, in the 2nd tertile with Lp-PLA2 values between 101 and 138 μg/L and in the 1st tertile (Lp-PLA2 values < 101 μg/L) regarding age, male gender, smoking habits, family history of CAD or history of a previous myocardial infarction, diabetes mellitus, arterial hypertension, hyperlipidemia, duration of CAD and treatment with relevant medication. Importantly, subjects with Lp-PLA2 values in the highest tertile, had significantly reduced FMD values compared to the middle and lower tertile (4.43 ± 2.37% vs. 4.61 ± 1.97% vs. 5.20 ± 2.52% respectively, P = 0.03). Patients in the highest tertile of Lp-PLA2 values had significantly higher AIx values (24.65 ± 8.69% vs. 23.33 ± 9.65%, P = 0.03), in comparison to the lowest tertile, with Lp-PLA2 values < 101 μg/L. A linear regression analysis showed that Lp-PLA2 values > 138 μg/L negatively correlated to FMD [b = - 0.45 (95% CI: - 0.79 - -0.11), P = 0.01] and AIx values [b = 1.81 (95% CI: 0.57-3.05), P < 0.001] independently of cofounders like gender, age, diabetes mellitus, arterial hypertension, dyslipidemia, smoking habits, family history of CAD, history of previous myocardial infarction, serum glucose, circulating lipid levels, duration of CAD, antihypertensive medication, antidiabetic drugs, statin therapy and treatment with β-blockers.ConclusionsElevated Lp-PLA2 levels relate to endothelial dysfunction and arterial stiffness in patients with stable CAD independently from classical risk factors for CAD, statin use, antihypertensive treatment, and duration of the disease.

Dataset Information

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

Publications

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

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