The Notch signaling pathway in retinal dysplasia and retina vascular homeostasis

The retina is one of the most essential elements of vision pathway in vertebrate. The dysplasia of retina cause congenital blindness or vision disability in individuals, and the misbalance in adult retinal vascular homeostasis leads to neo adults, such as diabetic retinopathy or age-related macular degeneration. Many developmental signaling pathways are involved in the process of retinal development and vascular homeostasis. Among them, Notch signaling pathway has long been studied, and Notch signaling-interfered mouse models show both neural retina dysplasia and vascular abnormality. In this review, we discuss the roles of Notch signaling in the maintenance of retinal progenitor cells, specification of retinal neurons and glial cells, and the sustaining of retina vascular homeostasis, especially from the aspects of conditional knockout mouse models. The potential of Notch signal manipulation may provide a powerful cell fate- and neovascularization-controUing tool that could have important applications in treatment of retinal diseases.

The FGF21-adiponectin axis in controlling energy and vascular homeostasis

Whole-body energy metabolism and cardiovascular homeostasis are tightly controlled processes that involve highly coordinated crosstalk among distal organs.This is mainly achieved by a large number of hormones released from each organ.Among them,fibroblast growth factor 21(FGF21)and adiponectin have recently gained considerable attention,since both of them possess multiple profound protective effects against a myriad of cardio-metabolic disorders.Despite their distinct structuresand production sites,these two hormones share striking functional similarity.This dichotomy is recently reconciled by the demonstration of the FGF21-adiponectin axis.In adipocytes,both transcription and secretion of adiponectin are strongly induced by FGF21,which is partially dependent on PPARg activity.Furthermore,the glucose-lowering,lipid-clearing,and anti-atherosclerotic functions of FGF21 are diminished in adiponectin-null mice,suggesting that adiponectin serves as an obligatory mediator of FGF21-elicited metabolic and vascular benefits.However,in both animals and human subjects with obesity,circulating FGF21 levels are increased whereas plasma adiponectin concentrations are reduced,perhaps due to FGF21 resistance,suggesting that dysfunctional FGF21-adiponectin axis is an important contributor to the pathogenesis of obesity-related cardio-metabolic syndrome.The FGF21-adiponectin axis protects against a cluster of cardio-metabolic disorders via mediating multi-organ communications,and is a promising target for therapeutic interventions of these chronic diseases.

Red Onion (Allium Cepa L.) Methanolic Extract Increases Extracellular Nucleotide Hydrolysis in Rat Serum

Ectonucleotidases are enzymes involved in nucleotides metabolism. The amount of circulating nucleotides may modulate distinct pathophysiological processes in the vasculature, including platelet aggregation and vascular tone. Onion (Allium cepa L.) phenolic compounds modulate enzymatic activity. The present study evaluated the total phenolic content of red onion methanolic extract, its antioxidant capacity, and its ability to interfere in nucleotides hydrolyses in rat serum. Total phenolic content was determined with the Folin-Ciocalteau reagent using gallic acid as a standard, while total flavonoid content was obtained through the aluminum chloride colorimetric method with quercetin as a standard. Antioxidant capacity was evaluated from the ability of the extract to scavenge ABTS·+ and DPPH· radicals. ATP, ADP, AMP, and p-Nph-5'-TMP hydrolyses were colorimetrically determined in response to different onion extract concentrations (0, 125, 250, 500, or 1000 μg/mL). Phenolic content of the extract was 54.35 mg GAE 100 g-1 sample, while flavonoid content was 7.22 mg quercetin g-1 sample. The IC50 value for ABTS·+ was 374.13 ± 7.52 μg/mL, while it was 440.29 ± 15.17 μg/mL for DPPH·. Red onion extract increased ADP and p-Nph-5'-TMP hydrolysis. The results confirmed that red onion contains high content of antioxidant, mainly flavonoids, and high antioxidant capacity. Additionally, biochemical studies suggest that the increased ADP breakdown may be important to regulate vascular processes. As it occurs for other enzymes, the antioxidant capacity of onion extract may neutralize reactive oxygen species (ROS) formation and favor ectonucleotidase activity and the hydrolysis of ADP, a major platelet agonist.

Mechanistic insight into lysyl oxidase in vascular remodeling and angiogenesis

Vascular remodeling and angiogenesis are two key processes in the maintenance of vascular homeostasis and involved in a wide array of vascular pathologies. Following these processes, extracellular matrix (ECM) provides the mechanical foundation for vascular walls. Lysyl oxidase (LOX), the key matrix-modifying enzyme, has been demonstrated to significantly affect structural abnormality and dysfunction in the blood vessels. The role of LOX in vascular remodeling and angiogenesis has always been the subject in the current medical research. Therefore, we presently make a summarization of the biosynthesis of LOX and the mechanisms involved in vascular remodeling and angiogenesis, as well as the role of LOX in diseases associated with vascular abnormalities and the therapeutic potential via targeting LOX. In particular, we give a proposal that LOX likely reshapes matrisome-associated genes expressions in the regulation of vascular remodeling and angiogenesis, which serves as a mechanistic insight into the critical role of LOX in these two aspects. Additionally, LOX has also dual effects on the vascular dysfunction, namely, inhibition of LOX for improving hypertension, restenosis and malignant tumor while activation of LOX for curing arterial aneurysm and dissection. LOX-targeted therapy may provide a promising therapeutic strategy for the treatment of various vascular pathologies associated with vascular remodeling and angiogenesis.