Elastin haploinsufficiency induces alternative aging processes in the aorta

Elastin, the main component of elastic fibers, is synthesized only in early life and provides the blood vessels with their elastic properties. With aging, elastin is progressively degraded, leading to arterial enlargement, stiffening, and dysfunction. Also, elastin is a key regulator of vascular smooth muscle cell proliferation and migration during development since heterozygous mutations in its gene (Eln) are responsible for a severe obstructive vascular disease, supravalvular aortic stenosis, isolated or associated to Williams syndrome. Here, we have studied whether early elastin synthesis could also influence the aging processes, by comparing the structure and function of ascending aorta from 6- and 24-month-old Eln+/- and Eln+/+ mice. Eln+/- animals have high blood pressure and arteries with smaller diameters and more rigid walls containing additional although thinner elastic lamellas. Nevertheless, longevity of these animals is unaffected. In young adult Eln+/- mice, some features resemble vascular aging of wild-type animals: cardiac hypertrophy, loss of elasticity of the arterial wall through enhanced fragmentation of the elastic fibers, and extracellular matrix accumulation in the aortic wall, in particular in the intima. In Eln+/- animals, we also observed an age-dependent alteration of endothelial vasorelaxant function. On the contrary, Eln+/- mice were protected from several classical consequences of aging visible in aged Eln+/+ mice, such as arterial wall thickening and alteration of alpha(1)-adrenoceptor-mediated vasoconstriction. Our results suggest that early elastin expression and organization modify arterial aging through their impact on both vascular cell physiology and structure and mechanics of blood vessels

ACTION OF VARIOUS ANTICOAGULANTS ON HEMOLYMPHS OF LOBSTERS AND SPINY LOBSTERS

Volume: 160Start Page: 55End Page: 6

COAGULATION IN THE CRAYFISH, ASTACUS LEPTODACTYLUS: ATTEMPTS TO IDENTIFY A FIBRINOGEN-LIKE FACTOR IN THE HEMOLYMPH

Volume: 151Start Page: 467End Page: 47

COMPARISON OF THE GRADIENT OF SETAL DEVELOPMENT OF UROPODS AND OF SCAPHOGNATHITES IN ASTACUS LEPTODACTYLUS

Volume: 155Start Page: 627End Page: 63

CD36 deficiency blunts effects of diet on regulatory T cells in murine gonadal adipose tissue and mesenteric lymph nodes

The effect of cluster of differentiation (CD)36 on regulatory T cells (Treg) was investigated in gonadal (GN) adipose tissues and mesenteric lymph nodes (MLN) of wild-type (WT) and CD36 deficient (CD36−/−) mice kept on standard fat (SFD, lean) or on high fat diet (HFD, obese). GN adipose tissue mass was smaller, but MLN size larger for obese CD36−/− versus obese WT mice. Overall, the reduction of Treg cells in GN adipose tissue and MLN after a HFD is much more prominent in WT than CD36−/− mice. Moreover, CD36−/− mice may be protected against obesity-related chronic inflammation.publisher: Elsevier articletitle: CD36 deficiency blunts effects of diet on regulatory T cells in murine gonadal adipose tissue and mesenteric lymph nodes journaltitle: Cellular Immunology articlelink: http://dx.doi.org/10.1016/j.cellimm.2015.08.006 content_type: article copyright: Copyright © 2015 Elsevier Inc. All rights reserved.status: publishe

The Anti-Adipogenic Potential of COUP-TFII Is Mediated by Downregulation of the Notch Target Gene Hey1

BACKGROUND: Chicken ovalbumin upstream promoter transcription factor II (COUP-TFII) belongs to the steroid/thyroid hormone receptor superfamily and may contribute to the pathogenesis of obesity. It has not conclusively been established, however, whether its role is pro- or anti-adipogenic. METHODS AND RESULTS: Gene silencing of Coup-tfII in 3T3-F442A preadipocytes resulted in enhanced differentiation into mature adipocytes. This was associated with upregulation of the Notch signaling target gene Hey1. A functional role of Hey1 was confirmed by gene silencing in 3T3-F442A preadipocytes, resulting in impaired differentiation. In vivo, de novo fat pad formation in NUDE mice was significantly stimulated following injection of preadipocytes with Coup-tfII gene silencing, but impaired with Hey1 gene silencing. Moreover, expression of Coup-tfII was lower and that of Hey1 higher in isolated adipocytes of obese as compared to lean adipose tissue. CONCLUSIONS: These in vitro and in vivo data support an anti-adipogenic role of COUP-TFII via downregulating the Notch signaling target gene Hey1.status: publishe

Les MAGUK : au-delà de l’accrochage des canaux ioniques

Les protéines appartenant à la famille des MAGUK (membrane associated guanylate kinase) jouent un rôle majeur dans l’organisation des régions spécialisées des membranes plasmiques comme les synapses neuronales, les zones d’adhérence des bordures épithéliales ou encore les disques intercalaires du myocarde. Cette famille comprend les protéines PSD95 (post-synaptic density 95), chapsyne 110, SAP102 (synapse-associated protein 102) ou encore SAP97. Elles possèdent toutes plusieurs domaines d’interaction protéique : domaines PDZ, SH3 et guanylate kinase sur lesquels viennent se fixer différents récepteurs, des canaux ioniques ou des constituants du cytosquelette, pour former de larges complexes protéiques. C’est le cas des canaux potassiques Kv qui présentent dans leur partie carboxy-terminale une séquence de type Thr/Ser-X-Val/Leu qui leur permet d’interagir avec les deux premiers domaines PDZ des MAGUK. Il reste maintenant à comprendre le rôle physiologique de ces protéines et à déterminer leur implication au cours de différents processus pathogènes

Adiposity and metabolic health in mice deficient in intestinal alkaline phosphatase

Intestinal alkaline phosphatase 3 (AKP3) is an enzyme that was reported to play a role in lipid metabolism and to prevent high fat diet-induced metabolic syndrome in mice. To investigate a potential functional role of AKP3 in diet-induced adiposity and metabolic health, we have kept male and female wild-type or AKP3 deficient mice on a high fat diet for 15 weeks to induce obesity and compared those with mice kept on standard fat diet. Body weight as well as adipose tissue mass were statistically significantly higher upon high fat diet feeding for mice of both genders and genotypes. Female mice of either genotype kept on high fat diet gained less weight, resulting in smaller adipose tissue depots with smaller adipocytes. However, AKP3 deficiency had no significant effect on body weight gain or adipose tissue mass and did not affect adipocyte size or density. Gene expression analysis revealed no effect of the genotype on inflammatory parameters in adipose tissue, except for tumor necrosis factor alpha, which was higher in mesenteric adipose tissue of female obese mice. Plasma glucose and insulin levels were also not affected in obese AKP3 deficient mice. Overall, our data do not support a functional role of AKP3 in adipose tissue development, or insulin sensitivity.status: publishe