The urotensin II receptor antagonist, urantide, protects against atherosclerosis in rats

Abstract

The aim of this study was to explore the use of urantide as an antagonist of the urotensin II (UII) receptor, G protein-coupled receptor 14 (GPR14), to protect against atherosclerosis (AS) in rats. The AS rat model was induced by an intraperitoneal injection of vitamin D3 (VD3) into rats fed with a high-fat diet for four weeks. Urantide was then injected into the rats. Immunohistochemical staining, serum biochemical assay, reverse transcription-polymerase chain reaction (RT-PCR) and western blotting were used to investigate the expression of UII and its receptor GPR14 in the AS rat model. Four weeks after induction, pathological changes typical of AS were observed in the AS rat model. In the plaques of the aortic tunica intima and tunica media, expression of UII and GPR14 was observed. The protein and gene expression levels of UII and GPR14 in the model group were significantly increased compared with those in the normal group (P<0.01). Urantide ameliorated the pathological changes of AS in the rat model and reduced the gene and protein expression levels of UII and GPR14 (P<0.05 or P<0.01). UII is associated with AS and the UII receptor GPR14-specific antagonist, urantide, demonstrates the ability to protect against AS. Thus, this study provides new insight and experimental theories for the clinical application of urantide to treat AS.

Elucidation of mechanisms of actions of thymoquinone-enriched methanolic and volatile oil extracts from Nigella sativa against cardiovascular risk parameters in experimental hyperlipidemia

“…HDL is assumed a key lipoprotein that helps lipid removal from macrophage foam cells in the arterial wall, and thus protects LDL oxidation. Several studies have been performed using albino Wistar rats as experimental atherosclerosis model, and they found it suitable and effective model to be used in condition of hypercholesterolemia and atherosclerosis [27,28]. In the present study, we have performed gas chromatography (GC) analysis of the ME and VO, fractionated from NS seed oil and identified their constituents by using two different mass spectrometry (MS) libraries.…”

Structure–Activity Study of the Peptides P5U and Urantide by the Development of Analogues Containing Uncoded Amino Acids at Position 9

“…[14,15] In particular, the latter provides an intriguing tool in the field of alternative pharmacological strategies, because negative modulation of the urotensinergic system can be useful in the treatment of various diseases such as atherosclerosis [16] and colon cancer. [17] Therefore, the discovery and availability of various ligands that can finely modulate the UT might be helpful in clarifying the role of hU-II as a multipurpose peptide in mammalian pathophysiological functions.…”

Membrane-tethered peptides derived from intracellular loops 2 and 3 of the urotensin II receptor act as allosteric biased ligands

“…In humans, the urotensinergic system, composed of a class 1A G protein-coupled receptor (hUT), and two endogenous peptide ligands, urotensin II (UII; hUII = H-Glu-Thr-Pro-Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH) and urotensin II-related peptide (URP, H-Ala-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH), continues to represent a promising contemporary target for the treatment of several pathologies (1,2). Notably, multiple studies in animal models have suggested that UT antagonists may represent potential therapeutic agents for treating atherosclerosis (3)(4)(5)(6), pulmonary arterial hypertension (7)(8)(9), metabolic syndrome (4), and heart failure (10)(11)(12). However, in spite of such promise, clinical studies of UT antagonist drug candidates have had limited success due to a lack of efficacy in humans (1,2,13,14).…”