Deficiency of CCAAT/enhancer binding protein-epsilon reduces atherosclerotic lesions in LDLR-/- Mice

10.1371/journal.pone.0085341PLoS ONE91-POLN

Larkin-Ovchinnikov-Fulde-Ferrell state in quasi-one-dimensional superconductors

The properties of a quasi-one-dimensional (quasi-1D) superconductor with {\it an open Fermi surface} are expected to be unusual in a magnetic field. On the one hand, the quasi-1D structure of the Fermi surface strongly favors the formation of a non-uniform state (Larkin-Ovchinnikov-Fulde-Ferrell (LOFF) state) in the presence of a magnetic field acting on the electron spins. On the other hand, a magnetic field acting on an open Fermi surface induces a dimensional crossover by confining the electronic wave-functions wave-functions along the chains of highest conductivity, which results in a divergence of the orbital critical field and in a stabilization at low temperature of a cascade of superconducting phases separated by first order transistions. In this paper, we study the phase diagram as a function of the anisotropy. We discuss in details the experimental situation in the quasi-1D organic conductors of the Bechgaard salts family and argue that they appear as good candidates for the observation of the LOFF state, provided that their anisotropy is large enough. Recent experiments on the organic quasi-1D superconductor (TMTSF)$_2$ClO$_4$ are in agreement with the results obtained in this paper and could be interpreted as a signature of a high-field superconducting phase. We also point out the possibility to observe a LOFF state in some quasi-2D organic superconductors.Comment: 24 pages+17 figures (upon request), RevTex, ORSAY-LPS-24109

Biochemical and genetic association of plasma apolipoprotein A-II levels with familial combined hyperlipidemia

Biochemical and genetic association of plasma apolipoprotein A-II levels with familial combined hyperlipidemia. Allayee H, Castellani LW, Cantor RM, de Bruin TW, Lusis AJ. Department of Human Genetics, Gonda Genetics Research Center, of California, Los Angeles, Calif 90095, USA. [email protected] Apolipoprotein A-II (apoA-II) is a major protein on high-density lipoprotein (HDL) particles, and in mice, its levels are associated with triglyceride and glucose metabolism. In particular, transgenic mice overexpressing apoA-II exhibit hypertriglyceridemia, increased body fat, and insulin resistance, whereas apoA-II-null mice have decreased triglycerides and increased insulin sensitivity. Given the phenotypic overlap between familial combined hyperlipidemia (FCH) and apoA-II transgenic mice, we investigated the relationship of apoA-II to this disorder. Despite having lower HDL-cholesterol (HDL-C), FCH subjects had higher apoA-II levels compared with unaffected relatives (P<0.00016). Triglyceride and HDL-C levels were significant predictors of apoA-II, demonstrating that apoA-II variation is associated with several FCH-related traits. After adjustment for multiple covariates, there was evidence for the heritability of apoA-II levels (h2=0.15; P<0.02) in this sample. A genome scan for apoA-II levels identified significant evidence (LOD=3.1) for linkage to a locus on chromosome 1q41, coincident with a suggestive linkage for triglycerides (LOD score=1.4). Thus, this locus may have pleiotropic effects on apoA-II and FCH traits. Our results demonstrate that apoA-II is biochemically and genetically associated with FCH and may serve as a useful marker for understanding the mechanism by which FCH develops

Autocrine VEGF maintains endothelial survival through regulation of metabolism and autophagy

Autocrine VEGF is necessary for endothelial survival, although the cellular mechanisms supporting this function are unknown. Here, we show that--even after full differentiation and maturation--continuous expression of VEGF by endothelial cells is needed to sustain vascular integrity and cellular viability. Depletion of VEGF from the endothelium results in mitochondria fragmentation and suppression of glucose metabolism, leading to increased autophagy that contributes to cell death. Gene-expression profiling showed that endothelial VEGF contributes to the regulation of cell cycle and mitochondrial gene clusters, as well as several--but not all--targets of the transcription factor FOXO1. Indeed, VEGF-deficient endothelium in vitro and in vivo showed increased levels of FOXO1 protein in the nucleus and cytoplasm. Silencing of FOXO1 in VEGF-depleted cells reversed expression profiles of several of the gene clusters that were de-regulated in VEGF knockdown, and rescued both cell death and autophagy phenotypes. Our data suggest that endothelial VEGF maintains vascular homeostasis through regulation of FOXO1 levels, thereby ensuring physiological metabolism and endothelial cell survival