Background:
Insulin resistance (IR) and diabetes mellitus (DM) are associated with increased risk of cardiovascular disease. We explored the specific effects of insulin resistance on vascular redox state and endothelial function in non-diabetic patients with coronary atherosclerosis.
Methods:
The study population consisted of 383 patients undergoing coronary bypass surgery (CABG). Endothelial function was estimated using non-invasive imaging (brachial Flow-Mediated Dilatation -FMD) preoperatively. During surgery, segments of human saphenous vein (SV)were obtained and used to quantify nitric oxide bioavailability (ex vivo vasorelaxations in response to acetylcholine) and NADPH oxidase-derived superoxide (O2-) by lucigenin chemiluminescence (using NADPH at 100μM). Glucose and insulin were measured in plasmas for calculation of HOMA-IR, the homeostatic model assessment of IR status.
Results:
The presence of IR (HOMA-IR>2.9) was associated with impaired FMD (A), reduced vasorelaxations of human vessels in response to acetylcholine (B) and elevated vascular O2- generation (C).
Conclusions:
IR is associated with impaired endothelial function and increased oxidative stress in human vessels. This is the first study demonstrating a direct effect of systemic insulin resistance on key mechanisms of atherogenesis in human vessels, highlighting it as a specific therapeutic target in non-diabetic patients with atherosclerosis.
Loss of Function in Heparan Sulfate Elongation Genes
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Results in Improved Nitric Oxide Bioavailability and Endothelial Function