Insulin resistance in spontaneously hypertensive rats is associated with endothelial dysfunction characterized by imbalance between NO and ET-1 production RID B-1970-2008

Insulin stimulates production of NO in vascular endothelium via activation of phosphatidylinositol (PI) 3-kinase, Akt, and endothelial NO synthase. We hypothesized that insulin resistance may cause imbalance between endothelial vasodilators and vasoconstrictors (e.g., NO and ET-1), leading to hypertension. Twelve-week-old male spontaneously hypertensive rats (SHR) were hypertensive and insulin resistant compared with control Wistar-Kyoto (WKY) rats (systolic blood pressure 202 +/- 11 vs. 132 +/- 10 mmHg; fasting plasma insulin 5 +/- 1 vs. 0.9 +/- 0.1 ng/ml; P < 0.001). In WKY rats, insulin stimulated dose-dependent relaxation of mesenteric arteries precontracted with norepinephrine (NE) ex vivo. This depended on intact endothelium and was blocked by genistein, wortmannin, or N(omega)-nitro-l-arginine methyl ester (inhibitors of tyrosine kinase, PI3-kinase, and NO synthases, respectively). Vasodilation in response to insulin (but not ACh) was impaired by 20% in SHR (vs. WKY, P < 0.005). Preincubation of arteries with insulin significantly reduced the contractile effect of NE by 20% in WKY but not SHR rats. In SHR, the effect of insulin to reduce NE-mediated vasoconstriction became evident when insulin pretreatment was accompanied by ET-1 receptor blockade (BQ-123, BQ-788). Similar results were observed during treatment with the MEK inhibitor PD-98059. In addition, insulin-stimulated secretion of ET-1 from primary endothelial cells was significantly reduced by pretreatment of cells with PD-98059 (but not wortmannin). We conclude that insulin resistance in SHR is accompanied by endothelial dysfunction in mesenteric vessels with impaired PI3-kinase-dependent NO production and enhanced MAPK-dependent ET-1 secretion. These results may reflect pathophysiology in other vascular beds that directly contribute to elevated peripheral vascular resistance and hypertension

TGF beta 3 induced chondroitin sulphate proteoglycan mediates palatal shelf adhesion

AbstractIn mammals, the adhesion and fusion of the palatal shelves are essential mechanisms in the development of the secondary palate. Failure of any of these processes leads to the formation of cleft palate. The mechanisms underlying palatal shelf adhesion are poorly understood, although the presence of filopodia on the apical surfaces of the superficial medial edge epithelial (MEE) cells seems to play an important role in the adhesion of the opposing MEE. We demonstrate here the appearance of chondroitin sulphate proteoglycan (CSPG) on the apical surface of MEE cells only immediately prior to contact between the palatal shelves. This apical CSPG has a functional role in palatal shelf adhesion, as either the alteration of CSPG synthesis by β-d-Xyloside or its specific digestion by chondroitinase AC strikingly alters the in vitro adhesion of palatal shelves. We also demonstrate the absence of this apical CSPG in the clefted palates of transforming growth factor beta 3 (TGF-β3) null mutant mice, and its induction, together with palatal shelf adhesion, when TGF-β3 is added to TGF-β3 null mutant palatal shelves in culture. When chick palatal shelves (that do not adherein vivo nor express TGF-β3, nor CSPG in the MEE) are cultured in vitro, they do not express CSPG and partially adhere, but when TGF-β3 is added to the media, they express CSPG and their adhesion increases strikingly. We therefore conclude that the expression of CSPG on the apical surface of MEE cells is a key factor in palatal shelf adhesion and that this expression is regulated by TGF-β3

Boosting the analytical properties of gold nanostars by single particle confinement into yolk porous silica shells

8 pags., 5 figs., 1 tab.Herein we illustrate an effective protocol to boost the optical enhancing properties of gold nanostars. By coating single nanostars with a mesoporous silica layer of the appropriate size (yolk capsules), to localize them under optical microscopy, it is possible to enumerate single particles and design SERS quantitative methods with minute amounts of metallic particles.N. P.-P., L. G., and M. A. C.-D. thank the MINECO-Spain (CTM2014-58481R, CTM2017-84050R, CTQ2017-88648R and RYC-2015-19107), Xunta de Galicia (Centro Singular de Investigacion de Galicia, Acc. 2016-19 and EM2014/035), Generalitat de Cataluña (2017SGR883), URV (2017PFRURV_B2-02), URV and Banco Santander (2017EXIT-08) and the European Union (ERDF). This project has received funding from the European Union’s Horizon 2020 research and innovation program under the MarieSkłodowska-Curie grant agreement No. 713679 and from the Universitat Rovira i Virgili. X. X. acknowledges the Lee Family Scholarship