Gender, metabolic control and carotid intima-media-thickness in children and adolescents with type 1 diabetes mellitus.

Background: Despite a marked improvement in the overall prognosis of patients with type 1 diabetes mellitus (T1DM), cardiovascular morbidity/mortality is still increased. Since cellular and microvascular aberrations have been demonstrated already in children with T1DM, albeit a good glycemic control (CO), we hypothesized that early macrovascular changes can be detected by common carotid artery intima-media thickness (CCA-IMT).

Methods: We included 73 children/adolescents with T1DM (34 boys, 39 girls; mean age, 14.

Influence of proton pump inhibitors and VKORC1 mutations on CYP2C9-mediated dose requirements of vitamin K antagonist therapy: a pilot study.

Interindividual variations in dose requirements of oral vitamin K antagonists (VKA) are attributed to several factors, including genetic variant alleles of vitamin K epoxide reductase complex subunit 1 (VKORC1) and cytochrome P450 2C9 (CYP2C9), but also interaction with co-medications. In this context, proton pump inhibitor (PPI)-related alterations of VKA maintenance dose requirements have been published. The present investigation aimed to test for an interaction profile of oral VKA-therapy and PPIs in relation to the CYP2C9 genotype.

Impact of age and gender on microvascular function.

Background: Microcirculatory function can be assessed by postocclusive reactive hyperaemia (PORH) using laser Doppler fluxmetry. Previous studies have shown that PORH reveals microvascular damage at an early stage. In particular, at younger ages, PORH might depend on age and gender.

CYP2C9 genotype and association with bone mineral density: a pilot study.

Background: In recent years reduced bone mineral density (BMD) and osteoporosis have become major public health problems. Single nucleotide polymorphisms (SNPs) in the cytochrome P450 2C9 (CYP2C9) gene influence the response to oral anticoagulant drugs, which are positively associated with the risk to develop osteoporosis. The aim of the present investigation was to clarify a potential role of CYP2C9 sequence variations and susceptibility to develop osteoporosis.

Familial hypercholesterolemia affects microvascular autoregulation in children.

Objective: Familial hypercholesterolemia (FH) impairs macrovascular endothelial function in childhood and causes an increase of cardiovascular risk in later life. Whether microvascular function is affected in children with FH is unknown. The aim of this study was to investigate the impact of FH on microvascular autoregulation in children by post occlusive reactive hyperemia (PORH).

Poor agreement in carotid artery stenosis detection by ultrasound between external offices and a vascular center.

Background: Carotid duplex ultrasonography is the prime investigation used to grade carotid artery stenosis in clinical routine. We compared the carotid ultrasound (US) scans performed externally with our results.

Materials And Methods: This retrospective study included 288 patients who had been referred to our outpatient department and initially presented with an external carotid duplex scan report indicating carotid atherosclerosis.

Microvascular function is impaired in children with morbid obesity.

Children's obesity is a growing problem in Western societies. We hypothesized that morbid obesity (body mass index [BMI] > 99.5th percentile) might affect microvascular function at an early stage.

Integrin cleavage regulates bidirectional signalling in vascular smooth muscle cells.

Integrins link the cytoskeleton to the extracellular matrix, providing outside-in/inside-out signalling essential for vascular smooth muscle cell (VSMC) migration in atherosclerosis. The integrin av subunit is synthesised from its precursor via furin-dependent endoproteolytic cleavage. Furin is a proprotein convertase (PC) highly expressed in VSMCs and in human atherosclerotic lesions.

Simvastatin reduces serum level of vascular endothelial growth factor in hypercholesterolemic patients.

Vascular endothelial growth factor plays a pivotal role in the progression of atherosclerotic lesions and causes instability of atherosclerotic plaques by inducing neoangiogenesis inside the current plaque. The pro-inflammatory cytokine interleukin (IL-) 6 induces vascular endothelial growth factor in smooth muscle cells (SMC). HMG-CoA reductase inhibitors (statins), display beside their lipid-lowering potency various pleiotropic effects.

Protein kinase C epsilon mediates angiotensin II-induced activation of beta1-integrins in cardiac fibroblasts.

Objective: Angiotensin II (AII) promotes cardiac fibrosis by increased extracellular matrix production and enhanced interaction of matrix proteins with their cellular receptors, including integrins. AII and other growth factors augment beta(1)-integrin-dependent adhesion and spreading by "inside-out signaling" without affecting the total number of integrin receptors. "Inside-out signaling" involves specific signaling pathways, including protein kinase C (PKC), leading to activation of beta1-integrins.

Proprotein convertases regulate insulin-like growth factor 1-induced membrane-type 1 matrix metalloproteinase in VSMCs via endoproteolytic activation of the insulin-like growth factor-1 receptor.

The IGF-1 receptor (IGF-1R) and MT1-MMP are synthesized as larger precursor proproteins, which require endoproteolytic activation by the proprotein convertases (PCs) furin/PC5 to gain full biological activity. The aim of this study was to investigate the contribution of PCs to IGF-1R and/or MT1-MMP activation in vascular smooth muscle cells (VSMCs) as well as VSMC proliferation/migration, which are key elements in vascular remodeling. Furin and PC5 mRNAs and proteins were found in VSMCs.

Regulation of matrix metalloproteinase MT1-MMP/MMP-2 in cardiac fibroblasts by TGF-beta1 involves furin-convertase.

Objective: Heart failure is characterized by an imbalance of matrix synthesis/turnover, finally resulting in fibrosis. Cardiac myocytes and fibroblasts play a pivotal role in the remodeling process. Cardiac remodeling involves the expression of TGF-beta1 and matrix metalloproteinases (MMPs) in cardiac fibroblasts (CFBs).

LPS regulate ERK1/2-dependent signaling in cardiac fibroblasts via PKC-mediated MKP-1 induction.

Activation of MAPK pathways by angiotensin II (Ang II) is important for cardiac fibroblast (CFB) proliferation and migration. Activity of MAP-kinases is closely controlled by a group of dual-specific MAP kinase phosphatases (MKPs). Lipopolysaccharides (LPS) and cytokines are elevated in patients with heart failure and may contribute to disease progression.