The tyrosine kinase inhibitor nilotinib targets discoidin domain receptor 2 in calcific aortic valve stenosis

Background and purpose: Tyrosine kinase inhibitors (TKI) used to treat chronic myeloid leukemia (CML) have been associated with cardiovascular side effects, including reports on calcific aortic valve stenosis. The aim of this study was to establish the effects of first and second generation TKIs in aortic valve stenosis, and to determine the...

Obeticholic Acid Modulates Serum Metabolites and Gene Signatures Characteristic of Human NASH and Attenuates Inflammation and Fibrosis Progression in Ldlr-/-.Leiden Mice

Concerns have been raised about whether preclinical models sufficiently mimic molecular disease processes observed in nonalcoholic steatohepatitis (NASH) patients, bringing into question their translational value in studies of therapeutic interventions in the process of NASH/fibrosis. We investigated the representation of molecular disease...

Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin

Background The residual risk that remains after statin treatment supports the addition of other LDL-C-lowering agents and has stimulated the search for secondary treatment targets. Epidemiological studies propose HDL-C as a possible candidate. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from atheroprotective HDL to...

Mirtoselect, an anthocyanin-rich bilberry extract, attenuates non-alcoholic steatohepatitis and associated fibrosis in ApoE∗3Leiden mice

Background & Aims Anthocyanins may have beneficial effects on lipid metabolism and inflammation and are demonstrated to have hepatoprotective properties in models of restraint-stress- and chemically-induced liver damage. However, their potential to protect against non-alcoholic steatohepatitis (NASH) under conditions relevant for human...

Distribution of perfluorooctanesulfonate and perfluorooctanoate into human plasma lipoprotein fractions

Some cross-sectional epidemiological studies have reported positive associations of serum concentrations of non-high density lipoprotein cholesterol with serum perfluorooctanesulfonate (PFOS) and perfluorooctanoate (PFOA). However, the strength of the reported associations is inconsistent for exposure–response across three orders of magnitude of...

Invasive properties of fibroblast-like synoviocytes Correlation with growth characteristics and expression of MMP-1 MMP-3 and MMP-10

Background: Matrix metalloproteinases (MMPs) have a pivotal role in the destruction of cartilage in rheumatoid arthritis (RA), which is mediated by the fibroblast-like synoviocytes (FLS). Objective: To examine the in vitro invasiveness of synoviocytes obtained from inflamed joints of patients with arthritis in relation to the expression of MMP 1...

Farnesyl pyrophosphate synthase is the molecular target of nitrogen-containing bisphosphonates

Bisphosphonates (Bps), inhibitors of osteoclastic bone resorption, are used in the treatment of skeletal disorders. Recent evidence indicated that farnesyl pyrophosphate (FPP) synthase and/or isopentenyl pyrophosphate (IPP) isomerase is the intracellular target(s) of bisphosphonate action. To examine which enzyme is specifically affected, we...

Inhibitors of protein: Arnesyl transferase and protein:geranylgeranyl transferase I : Synthesis of homologous diphosphonate analogs of isoprenylated pyrophosphate

Novel diphosphonate homologs 7a-7c, and their cyclic counterparts 8a- 8c, of the previously synthesized farnesyl pyrophosphate analogs 1 and 2 were prepared and tested for their inhibition potency and specificity of the enzymes PFT and PGGT-I. Compound 2 was shown to be the most potent inhibitor of PFT (1C50=0.58 ± 0.45 μM) in this series. The...