Objective—Synthesis of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthases, is strongly induced on immunostimulation in vascular endothelial cells (VECs). Expression of GTP cyclohydrolase I (GTPCH), the first enzyme in BH4 biosynthesis, is regulated by cytokines and considered rate-limiting. Herein we investigated the molecular mechanism and relevance of cytokine-depende...

BACKGROUND The prevalence of type 2 diabetes (T2D) among adults worldwide is rapidly increasing, and in patients with diabetes the major cause of death is macrovascular disease. Endothelial cells play an important role in maintaining vascular homeostasis. Free fatty acids, which are elevated in T2D, have previously been shown to induce endothelial dysfunction and apoptosis of endothelial cells,...

Our understanding of the molecular mechanism of atherosclerosis has changed during the past 20 years. A large variety of different risk factors such as smoking, shear stress, hypertension, hypercholesterolemia, diabetes mellitus, and obesity lead to endothelial activation and/or dysfunction, which can elicit a series of cellular interactions that culminate in the lesions of atherosclerosis. To ...

BACKGROUND CD40/CD40 ligand (CD40L) signaling is a potent activator of endothelial cells (ECs) and promoter of atherosclerosis. In this study, we investigate whether A20 (a gene we have shown to be antiinflammatory and antiapoptotic in ECs) can protect from CD40/CD40L-mediated EC activation. METHODS AND RESULTS Overexpression of CD40, in a transient transfection system, activates the transcri...

OBJECTIVE To determine whether non-enterobacterial endotoxins, which are likely to constitute the majority of the circulating endotoxin pool, may stimulate coronary artery endothelial cell activation. METHODS AND RESULTS Interleukin-8 secretion, monocyte adhesion, and E-selectin expression were measured in human umbilical vein endothelial cells (HUVECs) and coronary artery endothelial cells (...

OBJECTIVE Synthesis of tetrahydrobiopterin (BH4), an essential cofactor for nitric oxide synthases, is strongly induced on immunostimulation in vascular endothelial cells (VECs). Expression of GTP cyclohydrolase I (GTPCH), the first enzyme in BH4 biosynthesis, is regulated by cytokines and considered rate-limiting. Herein we investigated the molecular mechanism and relevance of cytokine-depende...

OBJECTIVE Activated mast cells (MCs) induce endothelial cell (EC) apoptosis in vitro and are present at sites of plaque erosions in vivo. To further elucidate the role of MCs in endothelial apoptosis and consequently in plaque erosion, we have studied the molecular mechanisms involved in MC-induced EC apoptosis. METHODS AND RESULTS Primary cultures of rat cardiac microvascular ECs (RCMECs) an...

OBJECTIVE LOX-1, a receptor for oxidized low-density lipoprotein, plays a critical role in atherosclerosis. Its expression is upregulated by pro-atherogenic stimuli, such as angiotensin II (Ang II). In this study, we explored LOX-1 transcriptional promoter activation in response to Ang II in human coronary artery endothelial cells (HCAECs). METHODS AND RESULTS We constructed full-length and d...

The proinflammatory cytokine interleukin (IL)-1 is expressed mainly within the endothelium of atherosclerotic plaques and may be linked with inflammatory mechanisms of atherogenesis. IL-1 action is complex and regulated in part by its naturally occurring inhibitor, the IL-1 receptor antagonist (IL-1ra). Therefore, we studied differential and specific isoform expression of IL-1ra in the endothel...

Abstract Introduction Obstructive sleep apnea syndrome (OSAS) is the most common disorder and it associated with arterial hypertension, heart failure, coronary artery disease as well atrial fibrillation. The underlying pathomechanisms for this association are only incompletely understood. In recent years long non-coding RNAs (lncRNA) have been shown to be involved in various cardiovascular path...