Effects of Low-Dose Colchicine on Serum High-Sensitivity C-Reactive Protein Level in Coronary Artery Disease Patients with Type 2 Diabetes Mellitus and Enhanced Inflammatory Response Protocol for a Randomized, Double-Blind, Placebo-Controlled, Phase 2, Dose-Finding Study.

Although cardiovascular mortality in Japan is lower than in other industrialized countries, clinical outcomes in coronary artery disease (CAD) patients with type 2 diabetes mellitus (T2DM) remain poor despite multiple evidence-based drug therapies and interventions. We assumed that part of residual risk in these patients may be attributable to enhanced inflammation, which can be inhibited presumably by colchicine. However, dose-responsiveness of anti-inflammatory effect of colchicine has not been elucidated.

Effect of short-term colchicine treatment on endothelial function in patients with coronary artery disease.

Background: Inflammation is associated with endothelial dysfunction and plays an important role in the pathogenesis and development of cardiovascular diseases. It has been shown that colchicine, an anti-inflammatory drug, improves the cardiovascular outcome in patients with cardiovascular disease. The purpose of this study was to evaluate the short-term effect of low-dose colchicine on endothelial function in patients with coronary artery disease (CAD).

Renin-Angiotensin System Inhibitors Can Prevent Intravenous Lipid Infusion-Induced Myocardial Microvascular Dysfunction and Leukocyte Activation.

Background: Levels of triglycerides and free fatty acids (FFAs) are elevated in patients with diabetes and may contribute to endothelial dysfunction through renin-angiotensin system (RAS) activation and oxidative stress. The present study investigated how systemic FFA loading affected myocardial microcirculation during hyperemia via RAS.

Methods and results: Eight healthy men received candesartan, perindopril, or a placebo for 2 days in a double-blind crossover design, and then myocardial microcirculation during hyperemia induced by a 2-h infusion of lipid/heparin was assessed using dipyridamole stress-myocardial contrast echocardiography (MCE).

Effects of Oral Antidiabetic Drugs on Changes in the Liver-to-Spleen Ratio on Computed Tomography and Inflammatory Biomarkers in Patients With Type 2 Diabetes and Nonalcoholic Fatty Liver Disease.

Purpose: Oral antidiabetic drugs (OADs) such as pioglitazone and metformin have beneficial effects in patients with nonalcoholic steatohepatitis. We prospectively assessed the effects of OADs on nonalcoholic fatty liver disease (NAFLD) in 886 men with type 2 diabetes mellitus and in a murine model of NAFLD.

Methods: Patients were randomized to receive pioglitazone, metformin, sitagliptin, or a non-OAD (control) for 6 months.

Peroxidized unsaturated fatty acids stimulate Toll-like receptor 4 signaling in endothelial cells.

Aim: Although unsaturated fatty acids are assumed to be protective against inflammatory disorders that include a pathway involving Toll-like receptor 4 (TLR4) activation, they might actually be toxic because of their high susceptibility to lipid peroxidation. Here we studied the effects of peroxidized unsaturated fatty acids on the TLR4-nuclear factor (NF)-κB pathway in endothelial cells.

Main Methods: Confluent cultured endothelial cells from bovine aorta were incubated for 1h with fatty acids integrated into phosphatidylcholine vesicles.

Dihydropyridine calcium channel blockers inhibit non-esterified-fatty-acid-induced endothelial and rheological dysfunction.

Circulating NEFAs (non-esterified fatty acids) from adipose tissue lipolysis lead to endothelial dysfunction and insulin resistance in patients with the metabolic syndrome or Type 2 diabetes mellitus. The aim of the present study was to test the hypothesis that DHP (dihydropyridine) CCBs (calcium channel blockers) prevent NEFA-induced endothelial and haemorheological dysfunction independently of their antihypertensive properties. Using a double-blind cross-over study design, nifedipine, amlodipine, diltiazem or placebo were administered to eight healthy subjects for 2 days before each study day.

Aldosterone enhances ligand-stimulated nitric oxide production in endothelial cells.

Chronic and acute actions of aldosterone have been shown recently to directly affect the cardiovascular system. However, it is unclear whether the acute effects of aldosterone on vasculature are constrictive or dilatory. Here, to clarify the nongenomic effects of aldosterone on endothelial function, we examined the effects of aldosterone on nitric oxide (NO) production in cultured endothelial cells (ECs) and on vascular tone.

Subcortical Ca2+ waves sneaking under the plasma membrane in endothelial cells.

Subplasmalemmal Ca2+, dynamically equilibrated with extracellular Ca2+, affects numerous signaling molecules, effectors, and events within this restricted space. We demonstrated the presence of a novel Ca2+ wave propagating beneath the plasma membrane in response to acute elevation of extracellular [Ca2+], by targeting a Ca2+ sensor, cameleon, to the endothelial plasmalemma. These subcortical waves, spatially distinct from classical cytosolic Ca2+ waves, originated in localized regions and propagated throughout the subplasmalemma.