Studies have shown that high-density lipoprotein (HDL)-raising compounds induce regression of aortic valve stenosis (AVS) in animal models. However, whether patients with AVS have an impaired HDL meta Show more
Studies have shown that high-density lipoprotein (HDL)-raising compounds induce regression of aortic valve stenosis (AVS) in animal models. However, whether patients with AVS have an impaired HDL metabolism is unknown. A total of 1435 single nucleotide polymorphisms in genes associated with HDL cholesterol levels (in or around GALNT2, LPL, ABCA1, APOA5, SCARB1, LIPC, CETP, LCAT, LIPG, APOC4, and PLTP) were genotyped in 382 patients with echocardiography-confirmed AVS (aortic jet velocity ≥2.5 m/s) and 401 controls. After control for multiple testing, none of the genetic variants showed a positive association with case/control status (adjusted P≥0.05 for all single nucleotide polymorphisms tested). In a subsample of this cohort, HDL cholesterol levels, apolipoprotein AI levels, lecithin-cholesterol acyltransferase activity, pre-β-HDL, HDL size, and 4 parameters of cholesterol efflux capacity were measured in apolipoprotein B-depleted serum samples from 86 patients with and 86 patients without AVS. Cholesterol efflux capacity was measured using J774 macrophages with and without stimulation of ATP-binding cassette A-1 expression by cAMP, and HepG2 hepatocytes for scavenger receptor class B type 1-mediated efflux. None of these parameters were different between cases and controls. However, compared with patients without coronary artery disease, sera from patients with coronary artery disease had lower HDL cholesterol levels, scavenger receptor class B type 1-mediated efflux, and HDL size (P≤0.003), independently of the presence or absence of AVS. Results of the present study suggest that, based on HDL genetics and HDL functionality, HDL metabolism does not seem to predict the risk of AVS. Because of our limited sample size, additional studies are needed to confirm these findings. Show less
Although CNS neurons have the potential to regenerate their axons after injury, myelin debris carrying axon growth inhibitors rapidly induce growth cone collapse. Receptors (NgR1, NgR2) and coreceptor Show more
Although CNS neurons have the potential to regenerate their axons after injury, myelin debris carrying axon growth inhibitors rapidly induce growth cone collapse. Receptors (NgR1, NgR2) and coreceptors (LINGO-1, p75(NTR), TROY) for these inhibitors have been characterized and transduction pathways partially identified. However, little is known about the expression of these receptors in intact and lesioned supraspinal projection neurons. Using in situ hybridization, immunohistochemistry and neuronal tract-tracing, we found that NgR1, NgR2 and LINGO-1 are strongly expressed in several neuronal populations of the adult mouse brain projecting to the spinal cord, including neurons projecting through the corticospinal, rubrospinal, caerulospinal, reticulospinal, raphespinal and vestibulospinal tracts. As expected, p75(NTR) expression was restricted to neuronal descending pathways from the brainstem. TROY was absent from most brain regions and from all neuronal projection systems, suggesting that additional signal-transducing coreceptors exist. Qualitative and quantitative analyses revealed that brain expression for these receptors was not affected by a severe T10 spinal cord contusion. Show less