Taking the structural information into account, we were able to tune the TEAD selectivity for a specific chemotype. However, different TEAD selectivity profiles did not affect the compound potency or efficacy in the NCI-H226 viability assay. Amides based on or analogues showed improved viability efficacy compared with the corresponding acids.
View Article and Find Full Text PDFBackground And Purpose: The purpose of this study was to evaluate the performance of magnetic resonance imaging (MRI) in measuring the optic nerve sheath diameter (ONSD) compared to the established method transorbital sonography (TOS) in patients with idiopathic intracranial hypertension (IIH).
Methods: Twenty-three patients with IIH were prospectively included applying IIH diagnostic criteria. All patients received a lumbar puncture with assessment of the cerebrospinal fluid (CSF) opening pressure to assure the IIH diagnosis.
Acta Crystallogr E Crystallogr Commun
July 2022
The title compound {systematic name: -2-[7-methyl-4-(4-methylphenyl)-4-(phenylimino)-6,6-bis(propan-2-yl)-3-oxa-4λ-thia-5-aza-6-silaoct-4-en-1-yl]-2,3-dihydro-1-isoindole-1,3-dione}, CHNOSSi, was synthesized by desoxychlorination of 4-methyl--phenyl-'-(triisopropyl-sil-yl)benzene-sul-fon-imid-am-ide and subsequent reaction with 2-(2-hy-droxy-eth-yl)isoindoline-1,3-dione. The racemic compound was crystallized from isopropanol. The structural characterization by single-crystal X-ray diffraction revealed two double-bonded nitro-gen atoms to the central sulfur atom and an overall crystal packing driven by its aromatic inter-actions.
View Article and Find Full Text PDFRadon is pervasive in our environment and the second leading cause of lung cancer induction after smoking. Therefore, the measurement of radon activity concentrations in homes is important. The use of charcoal is an easy and cost-efficient method for this purpose, as radon can bind to charcoal via Van der Waals interaction.
View Article and Find Full Text PDFEndothelial progenitor cells (EPCs) promote angiogenesis and play an important role in myocardial and vascular repair after ischemia and infarction. EPCs consist of different subpopulations including CD34‑CD133+ EPCs, which are precursors of more mature CD34+CD133+ EPCs and functionally more active in terms of homing and endothelial regeneration. In the present study we analyzed the functional and differentiation abilities of CD34‑CD133+ EPCs.
View Article and Find Full Text PDFObjectives: We aimed to characterize different cellular effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin 1 (AT1) receptor blockers (ARBs) as mono- or combination therapy in cardiac pressure overload. Methods and
Results: C57B1/6 mice received either the ACEI ramipril (2.5 mg/kg body weight), the ARB telmisartan (20 mg/kg body weight), or the combination.
Homing of endothelial progenitor cells (EPCs) is crucial for neoangiogenesis, which might be negatively affected by hypoxia. We investigated the influence of hypoxia on fibronectin binding integrins for migration and cell-matrix-adhesion. AMP-activated kinase (AMPK) and integrin-linked kinase (ILK) were examined as possible effectors of hypoxia.
View Article and Find Full Text PDFAims: Peripartum cardiomyopathy (PPCM) is associated with high mortality and morbidity. Endothelial damage involving cathepsin-D to form a 16 kDa prolactin (PRL) peptide is pathogenetically relevant. Inhibiting PRL peptide with bromocriptine has yielded promising results.
View Article and Find Full Text PDFAims: Collateral arteries protect tissue from ischaemia. Heart rate correlates with vascular events in patients with arterial obstructive disease. Here, we tested the effect of heart-rate reduction (HRR) on collateral artery growth.
View Article and Find Full Text PDFPostnatal vasculogenesis is mediated by endothelial progenitor cells (EPCs) which consist of subpopulations with different functional capacities. Our goal was to profile chemokine receptor expression on relevant subsets of EPCs and to characterize their role for effector functions. CD34(+)/CD133(+)/VEGFR2(+) EPCs were characterized by high expression of chemokine receptors CXCR4, CX3CR1, BLT1, and low level expression of CXCR2 and CCR2, while primordial CD34(-)/CD133(+)/VEGFR2(+) EPCs express these chemokine receptors at comparably low levels.
View Article and Find Full Text PDFInflammation and pro-hypertrophic signaling are important for development and progression of myocardial hypertrophy (LVH) and chronic heart failure (CHF). Here we investigated the relevance of integrin-linked kinase (ILK) for chemokine receptor CXCR4- and angiotensin II type 1-triggered signaling and its regulation and role in cardiac remodeling. Using ELISA, real-time-PCR, and Western blotting, the present study demonstrates that SDF-1 and its receptor CXCR4 are up-regulated in plasma and left ventricles, respectively, in mouse models of cardiac hypertrophy (transaortic constriction, transgenic cardiac-specific overexpression of rac1) and in human CHF in association with increased cardiac ILK-expression.
View Article and Find Full Text PDFIn patients with coronary artery disease (CAD), number and function of endothelial progenitor cells (EPCs) are down-regulated. The relevant intracellular signalling mechanisms responsible for dysfunction of EPCs in CAD remain poorly characterized. Our goal was to examine the regulation of ERK-1/2 by SDF-1 and the role of ERK-1/2 for adhesion in EPCs.
View Article and Find Full Text PDFNumber and function of endothelial progenitor cells (EPCs) are down-regulated in patients with coronary artery disease (CAD). Integrin-linked kinase (ILK) is a signal and adaptor protein that regulates survival of mature endothelial cells and vascular development. Here we show that EPC dysfunction in patients with CAD is paralleled by down-regulation of ILK while restoration of ILK expression rescues the migratory defect of CAD-EPCs.
View Article and Find Full Text PDFNat Clin Pract Cardiovasc Med
February 2008
Biochem Biophys Res Commun
October 2006
Our goal was to characterize the role of integrin-linked kinase (ILK) in vascular smooth muscle cells (VSMC), which play a crucial role in atherogenesis. Transfection of VSMC with wild-type and dominant-negative ILK cDNA constructs revealed that ILK mediates migration and proliferation of VSMC but has no effect on VSMC survival. The pro-atherogenic mediator angiotensin II increases ILK protein expression and kinase activity while statin treatment down-regulates ILK in VSMC.
View Article and Find Full Text PDFClin Res Cardiol
February 2006
Results from the HOPE and EUROPA trials showed that ACE inhibitors lower cardiovascular mortality of patients with atherosclerosis and preserved left ventricular function. However, despite apparently adequate study design, the recently conducted PEACE trial detected no benefit of an additional ACE inhibitor treatment in patients with coronary artery disease and no heart failure with respect to cardiovascular risk reduction. One of the main reasons for this discrepancy might be the lower cardiovascular baseline risk of the PEACE study population, which was more intensively treated with lipid lowering drugs and myocardial revascularization prior to enrollment than patients in HOPE or EUROPA.
View Article and Find Full Text PDFOur goal was to identify functionally important subpopulations within the heterogenous group of endothelial progenitor cells (EPC). Fluorescence-activated cell sorter analysis of CD133+ progenitor cells revealed the presence of CD34+ and CD34- subpopulations. CD34-/133+ progenitors differentiate into CD34+/133+ EPC, adhere more potently than these in response to SDF-1, and rapidly home to sites of limb ischemia in human volunteers.
View Article and Find Full Text PDFEstrogens confer atheroprotective effects that remain poorly understood. We hypothesised that estrogens directly target monocytes, and investigated the pathways via which estrogens might impact on monocyte adhesion. In an in vitro model of the vasculature (parallel plate laminar flow chamber, 2 dynes/cm2), 17beta-estradiol (24 h, 0.
View Article and Find Full Text PDFEndothelial progenitor cells (EPCs) have been implicated in the pathogenesis and treatment of cardiovascular disease. By use of quantitative uptake of DiLDL and lectin staining, EPCs have been characterized reliably. However, the exact nature and function of this cell population still remains poorly defined.
View Article and Find Full Text PDFThe development of tumor vasculature is thought to occur through two complementary processes: sprouting angiogenesis from preexisting blood vessels of the host, and vasculogenesis, which involves the spontaneous development of vessels through specific recruitment, differentiation, and vascular incorporation of circulating endothelial cells (EC), endothelial progenitor cells (EPC), or potentially bone marrow-derived cells. Recent reports, however, have challenged the belief that bone marrow-derived cells contribute to tumor neovascularization, claiming an exclusive role for sprouting angiogenesis in tumor blood vessel development. In the present study, we explored the recruitment behavior of bone marrow-derived lin(-)c-kit(+)Sca-1+ stem cells to subcutaneously implanted Lewis lung carcinoma in a syngeneic bone marrow transplantation model.
View Article and Find Full Text PDFIntegrin-linked kinase (ILK) is a phosphoinositide 3-kinase-dependent serine/threonine kinase that interacts with beta integrins. Here we show that endothelial cell (EC)-specific deletion of ILK in mice confers placental insufficiency with decreased labyrinthine vascularization, yielding no viable offspring. Deletion of ILK in zebra fish using antisense morpholino oligonucleotides results in marked patterning abnormalities of the vasculature and is similarly lethal.
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