Role of endothelial Nox2 NADPH oxidase in angiotensin II-induced hypertension and vasomotor dysfunction

NADPH oxidase (Nox)-derived reactive oxygen species (ROS) are known to be involved in angiotensin II-induced hypertension and endothelial dysfunction. Several Nox isoforms are expressed in the vessel wall, among which Nox2 is especially abundant in the endothelium. Endothelial Nox2 levels rise during hypertension but little is known about the cell-specific role of endothelial Nox2 in vivo. To address this question, we generated transgenic mice with endothelial-specific overexpression of Nox2 (Tg) and studied the effects on endothelial function and blood pressure. Tg had an about twofold increase in endothelial Nox2 levels which was accompanied by an increase in p22phox levels but no change in levels of other Nox isoforms or endothelial nitric oxide synthase (eNOS). Basal NADPH oxidase activity, endothelial function and blood pressure were unaltered in Tg compared to wild-type littermates. Angiotensin II caused a greater increase in ROS production in Tg compared to wild-type aorta and attenuated acetylcholine-induced vasorelaxation. Both low and high dose chronic angiotensin II infusion increased telemetric ambulatory blood pressure more in Tg compared to wild-type, but with different patterns of BP change and aortic remodeling depending upon the dose of angiotensin II dose. These results indicate that an increase in endothelial Nox2 levels contributes to angiotensin II-induced endothelial dysfunction, vascular remodeling and hypertension

Betacellulin Induces Increased Retinal Vascular Permeability in Mice

BACKGROUND: Diabetic maculopathy, the leading cause of vision loss in patients with type 2 diabetes, is characterized by hyper-permeability of retinal blood vessels with subsequent formation of macular edema and hard exudates. The degree of hyperglycemia and duration of diabetes have been suggested to be good predictors of retinal complications. Intervention studies have determined that while intensive treatment of diabetes reduced the development of proliferative diabetic retinopathy it was associated with a two to three-fold increased risk of severe hypoglycemia. Thus we hypothesized the need to identify downstream glycemic targets, which induce retinal vascular permeability that could be targeted therapeutically without the additional risks associated with intensive treatment of the hyperglycemia. Betacellulin is a 32 kD member of the epidermal growth factor family with mitogenic properties for the retinal pigment epithelial cells. This led us to hypothesize a role for betacellulin in the retinal vascular complications associated with diabetes. METHODS AND FINDINGS: In this study, using a mouse model of diabetes, we demonstrate that diabetic mice have accentuated retinal vascular permeability with a concomitant increased expression of a cleaved soluble form of betacellulin (s-Btc) in the retina. Intravitreal injection of soluble betacellulin induced retinal vascular permeability in normoglycemic and hyperglycemic mice. Western blot analysis of retinas from patients with diabetic retinopathy showed an increase in the active soluble form of betacellulin. In addition, an increase in the levels of A disintegrin and metalloproteinase (ADAM)-10 which plays a role in the cleavage of betacellulin was seen in the retinas of diabetic mice and humans. CONCLUSIONS: These results suggest that excessive amounts of betacellulin in the retina may contribute to the pathogenesis of diabetic macular edema

Not Available

Not AvailableGymnema sylvestre is an important medicinal plant containing antidiabetic activity. Through de novo transcriptomic study, the pathways of polyoxypregnane glycosides were explored and candidate genes of these pathways were identified in G. sylvestre. High-quality raw reads were assembled into transcripts which resulted in 193,615 unigenes. These unigenes further decoded 58,274 coding DNA sequences (CDSs). Functional annotation of predicted CDSs was carried out using the protein databases, i.e., NCBI’s non-redundant, Uniprot and Pfam. Eukaryotic orthologous group (KOG) classification and transcription factor analysis has revealed most CDS-enriched categories as “Signal transduction mechanism” and “Basic Helix loop helix” (bHLH) transcription factor family, respectively. A total of 16,569 CDSs were assigned minimum one Gene Ontology (GO) term. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis disclosed 235 CDSs which represented total 27 genes of pregnane glycoside pathways and 19 CDSs represented 10 important enzymes of polyoxypregnane glycoside biosynthesis, i.e., sterol 24-C-methyltransferase, cycloeucalenol cycloisomerase, Δ14-sterol reductase, C-8,7 sterol isomerase, sterol methyltransferase 2, C-5 sterol desaturase, sterol Δ7 reductase, Δ24 sterol reductase, 3β-hydroxysteroid dehydrogenase and progesterone 5β reductase (5βPOR). This transcriptome analysis provided an important resource for future functional genomic studies in G. sylvestre.GSBTM, GUJARA

De novo transcriptome analysis deciphered polyoxypregnane glycoside biosynthesis pathway in Gymnema sylvestre

Gymnema sylvestre is an important medicinal plant containing antidiabetic activity. Through de novo transcriptomic study,the pathways of polyoxypregnane glycosides were explored and candidate genes of these pathways were identified in G.sylvestre. High-quality raw reads were assembled into transcripts which resulted in 193,615 unigenes. These unigenes furtherdecoded 58,274 coding DNA sequences (CDSs). Functional annotation of predicted CDSs was carried out using the proteindatabases, i.e., NCBI’s non-redundant, Uniprot and Pfam. Eukaryotic orthologous group (KOG) classification and transcriptionfactor analysis has revealed most CDS-enriched categories as “Signal transduction mechanism” and “Basic Helix loophelix” (bHLH) transcription factor family, respectively. A total of 16,569 CDSs were assigned minimum one Gene Ontology(GO) term. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis disclosed 235 CDSs which representedtotal 27 genes of pregnane glycoside pathways and 19 CDSs represented 10 important enzymes of polyoxypregnane glycosidebiosynthesis, i.e., sterol 24-C-methyltransferase, cycloeucalenol cycloisomerase, Δ14-sterol reductase, C-8,7 sterol isomerase,sterol methyltransferase 2, C-5 sterol desaturase, sterol Δ7 reductase, Δ24 sterol reductase, 3β-hydroxysteroid dehydrogenaseand progesterone 5β reductase (5βPOR). This transcriptome analysis provided an important resource for future functionalgenomic studies in G. sylvestre

Preparation of nanocrystalline nickel oxide from nickel hydroxide using spark plasma sintering and inverse Hall-Petch related densification

Nanocrystalline nickel oxide (NiO) was prepared from nickel hydroxide by Spark plasma sintering (SPS) and the mechanisms involved in the densification of NiO were studied. Reverse precipitated nickel hydroxide powders were SPS processed at 400, 600 and 700 degrees C with 70 MPa pressure. Pure NiO with 12 nm crystallite size formed after 400 degrees C sintering process. However NiO grains had grown to 18 and 38 nm after 600 and 700 degrees C sintering respectively. NiO pellets prepared using 600 and 700 degrees C SPS sintering schedules had relative densities of 83% and 94% respectively. Two displacement rate regimes were observed during densification of NiO in both 600 and 700 degrees C sintering processes. Decomposition of nickel hydroxide and particle sliding of NiO led to first displacement rate maximum while inverse Hall-Petch based plastic deformation facilitated densification during the constant second displacement rate regime. No densification occurred during sintering holding times indicating the limited role that diffusion played during densification