Subtotal Nephrectomy Associated with a High-Phosphate Diet in Rats Mimics the Development of Calcified Aortic Valve Disease Associated with Chronic Renal Failure.

This study addressed the hypothesis that subtotal nephrectomy associated with a high-phosphorus diet (5/6Nx + P) in rats represents a suitable animal model to mimic the cardiovascular consequences of chronic kidney disease (CKD) including calcified aortic valve disease (CAVD). Indeed, the latter contributes to the high morbidity and mortality of CKD patients and sorely lacks preclinical models for pathophysiological and pharmacological studies. Renal and cardiovascular function and structure were compared between sham-operated and 5/6 Nx rats + P 10 to 12 weeks after surgery.

A Supraceliac Aortic Cross Clamping Model to Explore Remote Lung Injury and the Endothelial Glycocalyx.

Background: We hypothesized that supraceliac aortic cross clamping could induce lung injury mediated by an inflammatory ischemia-reperfusion (IR) trigger. We aimed to characterize glycocalyx (GCX), a component of endothelial membrane, participating to remote lung injury.

Methods: Rats underwent supraceliac aortic cross clamping for 40 min and were sacrificed at 0, 3, 6, and 24 hr of reperfusion (n = 10/group).

Targeting the Urotensin II/UT G Protein-Coupled Receptor to Counteract Angiogenesis and Mesenchymal Hypoxia/Necrosis in Glioblastoma.

Glioblastomas (GBMs) are the most common primary brain tumors characterized by strong invasiveness and angiogenesis. GBM cells and microenvironment secrete angiogenic factors and also express chemoattractant G protein-coupled receptors (GPCRs) to their advantage. We investigated the role of the vasoactive peptide urotensin II (UII) and its receptor UT on GBM angiogenesis and tested potential ligand/therapeutic options based on this system.

Urantide Improves Cardiac Function, Modulates Systemic Cytokine Response, and Increases Survival in A Murine Model of Endotoxic Shock.

Introduction: Urotensin II is a potent vasoactive peptide activating the the G protein-coupled urotensin II receptor UT, and is involved in systemic inflammation and cardiovascular functions. The aim of our work was to study the impact of the UT antagonist urantide on survival, systemic inflammation, and cardiac function during endotoxic shock.

Methods: C57Bl/6 mice were intraperitoneally injected with lipopolysaccharide (LPS) and then randomized to be injected either by urantide or NaCl 0.

Impact of high-fat diet and vitamin D supplementation on aortic stenosis establishment in waved-2 epidermal growth factor receptor mutant mice.

Objective: The use of animal models of aortic stenosis (AS) remains essential to further elucidate its pathophysiology and to evaluate new therapeutic strategies. The waved-2 mouse AS model has been proposed; data have indicated that while aortic regurgitation (AR) is effectively induced, development of AS is rare. We aimed to evaluate the effect of high-fat diet (HFD) and vitamin D supplementation in this model.

Chemotactic G protein-coupled receptors control cell migration by repressing autophagosome biogenesis.

Chemotactic migration is a fundamental behavior of cells and its regulation is particularly relevant in physiological processes such as organogenesis and angiogenesis, as well as in pathological processes such as tumor metastasis. The majority of chemotactic stimuli activate cell surface receptors that belong to the G protein-coupled receptor (GPCR) superfamily. Although the autophagy machinery has been shown to play a role in cell migration, its mode of regulation by chemotactic GPCRs remains largely unexplored.

Hypothalamic, thalamic and hippocampal lesions in the mouse MCAO model: Potential involvement of deep cerebral arteries?

Intraluminal monofilament occlusion of the middle cerebral artery (MCAO) in mice is the most used rodent model to study the pathophysiology of stroke. However, this model often shows brain damage in regions not supplied by the MCA such as the hypothalamus, hippocampus and thalamus. Several studies have suggested some explanations on these localized infarcts.

Kondrat'eva ligation: Diels-Alder-based irreversible reaction for bioconjugation.

Diversification of existing chemoselective ligations is required to efficiently access complex and well-defined biomolecular assemblies with unique and valuable properties. The development and bioconjugation applications of a novel Diels-Alder-based irreversible site-specific ligation are reported. The strategy is based on a Kondrat'eva cycloaddition between bioinert and readily functionalizable 5-alkoxyoxazoles and maleimides that readily react together under mild and easily tunable reaction conditions to afford a fully stable pyridine scaffold.

Biased signaling regulates the pleiotropic effects of the urotensin II receptor to modulate its cellular behaviors.

Biased agonism by G-protein-coupled receptor ligands has opened up strategies for targeted physiological or therapeutic actions. We hypothesized that urotensin II (UII)-derived peptides displayed unexpected physiological effects because of such biased signaling on the UII human urotensin (hUT) receptor. We determined the coupling to G proteins and β-arrestins of the UII-activated hUT receptor expressed in HEK293 using bioluminescence resonance energy transfer (BRET) biosensors, as well as the production of IP1-3 and cAMP using homogenous time-resolved Forster resonance energy transfer (FRET) (HTRF)-based assays.