Comparative study between high-dose fluvastatin and low-dose fluvastatin and ezetimibe with regard to the effect on endothelial function in diabetic patients.

It is well established that statins improve the prognosis of patients with coronary artery disease. However, it is still unclear whether the protective effects of statins relate to lipid lowering alone or whether other pleiotropic effects may contribute. Thus, we compared the endothelial function among two groups of diabetic patients treated with fluvastatin 60 mg (F60) or fluvastatin 20 mg combined with ezetimibe 10 mg (F20/E10).

Fenofibrate suppresses microvascular inflammation and apoptosis through adenosine monophosphate-activated protein kinase activation.

The Fenofibrate Intervention and Event Lowering in Diabetes study demonstrated that treatment with fenofibrate in individuals with type 2 diabetes mellitus not only reduced nonfatal coronary events but also diminished the need for laser treatment of diabetic retinopathy and delayed the progression of diabetic nephropathy. However, the mechanism by which fenofibrate may have altered the microvasculature remains unclear. We thus investigated the effect of fenofibrate on human glomerular microvascular endothelial cells (HGMEC).

An ACTH-secreting pituitary adenoma within the sphenoid sinus.

A 68-year-old woman developed Cushingoid features three months prior to admission. She was found to have a markedly elevated plasma ACTH-cortisol level. Magnetic resonance imaging (MRI) revealed a mass in the left sphenoidal sinus, which had become enlarged to a point where it could not be removed by transsphenoidal surgery.

Anti-inflammatory role of cilostazol in vascular smooth muscle cells in vitro and in vivo.

Aim: Cilostazol is a selective inhibitor of phosphodiesterase 3, by which it increases intracellular cAMP and activates protein kinase A, thereby inhibiting platelet aggregation and inducing peripheral vasodilation. We investigated whether cilostazol might prevent nuclear factor (NF)-kappaB activation by activating AMP-activated protein kinase (AMPK) in vascular smooth muscle cells (VSMC).

Methods And Results: Cilostazol was observed to activate AMPK, as well as its downstream target, acetyl-CoA carboxylase, in rat VSMC.

Induction of gene expression in response to globular adiponectin in vascular endothelial cells.

Aims: Adiponectin is an adipocyte-specific protein that plays an important regulatory role in the development or prevention of diabetes and atherosclerosis.

Main Methods: In the present study, we examined the effect of a proteolytic cleavage product of adiponectin, known as globular adiponectin (gAd), on induction of gene expression and activation of various signaling pathways in vascular endothelial cells.

Key Findings: We showed that gAd induces the expression of a number of genes using PCR arrays, including MCP-1, VCAM-1, E-selectin, IL-6, and IL-8, all of which have been previously shown to be associated with adiponectin, as well as SOD2, PAI-1, and CSF2, which is a new finding.

Cilostazol inhibits cytokine-induced nuclear factor-kappaB activation via AMP-activated protein kinase activation in vascular endothelial cells.

Aims: Cilostazol is a selective inhibitor of phosphodiesterase 3 that increases intracellular cyclic AMP (cAMP) levels and activates protein kinase A, thereby inhibiting platelet aggregation and inducing peripheral vasodilation. We hypothesized that cilostazol may prevent inflammatory cytokine induced-nuclear factor (NF)-kappaB activation by activating AMP-activated protein kinase (AMPK) in vascular endothelial cells.

Methods And Results: Cilostazol was observed to activate AMPK and its downstream target, acetyl-CoA carboxylase, in human umbilical vein endothelial cells (HUVEC).

Adiponectin induces NF-kappaB activation that leads to suppression of cytokine-induced NF-kappaB activation in vascular endothelial cells: globular adiponectin vs. high molecular weight adiponectin.

Adiponectin circulates in plasma as various isoforms. However, the biological activity of each isoform has not been firmly established. High molecular weight (HMW) adiponectin may be the active form of adiponectin, while a proteolytic cleavage product of adiponectin, known as globular adiponectin (gAd), has recently been shown to activate vascular endothelial cells.

High molecular weight adiponectin activates AMPK and suppresses cytokine-induced NF-kappaB activation in vascular endothelial cells.

Various isoforms of adiponectin circulate in the plasma. We purified high molecular weight (HMW) adiponectin from human plasma. HMW adiponectin was observed to activate AMP-activated protein kinase (AMPK), thereby increasing the phosphorylation of eNOS and NO production in endothelial cells.

PPARalpha activators upregulate eNOS activity and inhibit cytokine-induced NF-kappaB activation through AMP-activated protein kinase activation.

Endothelium-derived NO is an important mediator of vascular protection and adhesion molecule expression on the endothelial cell surface is critical for leukocyte recruitment to atherosclerotic lesions. We hypothesized that AMP-activated protein kinase (AMPK) activity is a down-stream mediator of the beneficial effects of PPARalpha activators on vascular endothelial cells. Treatment of human umbilical vein endothelial cells (HUVEC) with fenofibrate or WY14643 resulted in transient activation of AMPK, as monitored by phosphorylation of AMPK and its down-stream target, acetyl-CoA carboxylase.

Globular adiponectin induces adhesion molecule expression through the sphingosine kinase pathway in vascular endothelial cells.

The signaling pathways that couple adiponectin receptors to functional, particularly inflammatory, responses have remained elusive. We report here that globular adiponectin induces endothelial cell activation, as measured by the expression of adhesion proteins such as vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin and MCP-1, through the sphingosine kinase (SKase) signaling pathway. Treatment of human umbilical vein endothelial cells with globular adiponectin resulted in NF-kappaB activation and increased mRNA levels of VCAM-1, ICAM-1, E-selectin and MCP-1.