Hypoadiponectinemia Is Associated with Impaired Endothelium-Dependent Vasodilation

Abstract

Adiponectin may have an antiatherogenic effect by reducing endothelial activation. We hypothesized that plasma adiponectin levels were correlated with endothelial function. Plasma adiponectin level was determined by an in-house RIA assay using a rabbit polyclonal antibody in 73 type 2 diabetic patients and 73 controls. Endothelium-dependent and independent vasodilation of the brachial artery was measured by high-resolution vascular ultrasound. Plasma adiponectin level was lower in diabetic patients than in controls (4.73 +/- 1.96 vs. 7.69 +/- 2.80 microg/ml, respectively; P < 0.001), and they also had impaired endothelium-dependent (5.6 +/- 3.6 vs. 8.6 +/- 4.5%, respectively; P < 0.001) and -independent vasodilation (13.3 +/- 4.9 vs. 16.5 +/- 5.6%, respectively; P < 0.001). Plasma adiponectin correlated with endothelium-dependent vasodilation in controls (P = 0.02) and diabetic patients (P = 0.04). On general linear-model univariate analysis, brachial artery diameter, the presence of diabetes, plasma adiponectin, and high-density lipoprotein were significant independent determinants of endothelium-dependent vasodilation. In vitro experiments showed that endothelial cells expressed adiponectin receptors, and adiponectin increased nitric oxide production in human aortic endothelial cells. In conclusion, low plasma adiponectin level is associated with impaired endothelium-dependent vasodilation, and the association is independent of diabetes mellitus. Adiponectin may act as a link between adipose tissue and the vasculature.

The role of total and high-molecular-weight complex of adiponectin in vascular function in offspring whose parents both had type 2 diabetes

“…The link between HDL-cholesterol and EDV that we demonstrate is well established: multiple studies show low HDLcholesterol is highly predictive of endothelial dysfunction in healthy and diabetic subjects [49][50][51][52][53], and in experimental models where HDL-cholesterol is raised acutely, EDV normalises [58]. Thus, the role of HDL-cholesterol as a potential confounder in the relationship between adiponectin and endothelial function in vivo may not have been adequately considered in previous reports [25,27]. In future studies, the relationship between adiponectin and EDV needs to be carefully controlled for HDL-cholesterol, which correlates highly with both adiponectin and EDV and is therefore a potential important confounding variable.…”

“…A positive relationship between adiponectin and peak forearm blood flow was found in both healthy [25] and hypertensive Japanese subjects [26]. Tan et al described a positive relationship between adiponectin and EDV both in healthy and in type 2 diabetic persons [27]. In contrast, Singhal et al [54] reported no correlation between flow-mediated endothelial-dependent vasodilation and adiponectin in adolescents with normal BMI, and Fernandez-Real et al found no correlation between adiponectin in EDV in persons with either normal or impaired glucose tolerance [28].…”

“…In brief, after an overnight fast and the collection of baseline samples, Dextrose 0.3 g/kg was administered intravenously, followed 20 min later by the intravenous infusion of insulin 0.03 U/kg (Humulin R; Eli Lilly, Indianapolis, IN, USA). Samples were collected for insulin and glucose at 2, 3, 4, 5,6,8,10,12,14,19,22,23,24,25,27,30,40,50,60,70,80, 90, 100, 120, 140, 160 and 180 min following the dextrose and analysed using the Bergman's Minimal Model, a computer-based method to assess plasma insulin and glucose dynamics during an IVGTT. The minimum model for glucose disposal and insulin dynamics yields assessments of insulin secretion and sensitivity, including the insulin sensitivity index (S I ) and the glucose effectiveness index (S G ) also known as insulin-independent glucose clearance.…”

“…Given the experimental evidence supporting an antiatherogenic property of adiponectin, it has been proposed that a link between this protein and endothelial dysfunction may exist [25][26][27][28]. However, the nature of this association remains poorly characterised.…”

Association of resistin and adiponectin with different clinical blood pressure phenotypes

“…2 Adipose tissue traditionally represents a depot for storing excess of energy in the form of triglycerides and resembles a secreting organ of hormones and molecular mediators with multi-systemic physiological actions including the vasculature. 3 Resistin (Res) and adiponectin (Adp) are two adiposesecreted signals with apparently opposite functions regarding the control of insulin sensitivity, 4,5 regulation of endothelial function 6,7 and systemic inflammatory load. 8,9 Although there is a bidirectional association between endothelial dysfunction and sub-clinical inflammation with increased haemodynamic load, 10 it is yet unknown whether the actions of Res and Adp on the vasculature are translated into elevated BP; however, previous studies have shown that Res 11,12 and Adp 13 are correlated with hypertension, but these studies have not been focused on ambulatory BP measurements.…”