Urotensin-II As a Promising Key-Point of Cardiovascular Disturbances Sequel

Avagimyan, Ashot; Albina, Kajaia; Gabunia, Luiza; Ghambashidze, Ketevan; Sulashvili, Nodar; Heshmat-Ghahdarijani, Kiyan; Sheibani, Mohammad; Aznauryan, Artashes

doi:10.1016/j.cpcardiol.2021.101074

Cited by 7 publications

(2 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, it was shown that UII may play an important role in the central mechanisms of blood pressure regulation. It was implied that UII participates in the complex functional reorganization of neuronal formations in the central nervous system, which may consequently lead to the occurrence of hypertension [ 42 ]. Furthermore, a study by Alicic et al, as well as several other studies, determined a positive correlation between UII levels and blood pressure, with a vasoconstrictive effect as a probable mechanism of action [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

Serum Urotensin II Levels Are Elevated in Patients with Obstructive Sleep Apnea

et al. 2023

View full text Add to dashboard Cite

Obstructive sleep apnea (OSA) has become major public concern and is continuously investigated in new aspects of pathophysiology and management. Urotensin II (UII) is a powerful vasoconstrictor with a role in cardiovascular diseases. The main goal of this study was to evaluate serum UII levels in OSA patients and matched controls. A total of 89 OSA patients and 89 controls were consecutively enrolled. A medical history review and physical examination of the participants was conducted, with polysomnography performed in the investigated group. UII levels and other biochemical parameters were assessed according to the standard laboratory protocols. The median AHI in the OSA group was 39.0 (31.4–55.2) events/h, and they had higher levels of hsCRP when compared to control group (2.87 ± 0.71 vs. 1.52 ± 0.68 mg/L; p < 0.001). Additionally, serum UII levels were significantly higher in the OSA group (3.41 ± 1.72 vs. 2.18 ± 1.36 ng/mL; p < 0.001), while positive correlation was found between UII levels and hsCRP (r = 0.450; p < 0.001) and systolic blood pressure (SPB) (r = 0.317; p < 0.001). Finally, multiple regression analysis showed significant association of UII levels with AHI (0.017 ± 0.006, p = 0.013), SBP (0.052 ± 0.008, p < 0.001) and hsCRP (0.538 ± 0.164, p = 0.001). As UII levels were associated with blood pressure and markers of inflammation and OSA severity, it might play an important role in the complex pathophysiology of OSA and its cardiometabolic complications.

show abstract

Section: Discussionmentioning

confidence: 99%

Serum Urotensin II Levels Are Elevated in Patients with Obstructive Sleep Apnea

et al. 2023

View full text Add to dashboard Cite

show abstract

“…The UT receptor and endogenous ligands are widely expressed in various tissues from fish to mammals [2,3]. Clinical studies have shown that U-II/UT expression levels are closely associated with a variety of diseases, such as cardiovascular [4], liver [5], and kidney diseases [6]. It has been suggested that U-II may play a key role in glucose and fat metabolism [7][8][9].…”

Section: Introductionmentioning

confidence: 99%

Combination of Docking-Based and Pharmacophore-Based Virtual Screening Identifies Novel Agonists That Target the Urotensin Receptor

Yin

Chen

et al. 2022

Molecules

View full text Add to dashboard Cite

The urotensin receptor (UT receptor), a G-protein-coupled receptor mediating urotensin-II and urotensin-II-related peptide signaling in the urotensinergic system, has multiple pharmacological activities. However, there is no drug targeting the UT receptor currently in clinical use, and the discovery of new leads is still important. The complete crystal structure of the UT receptor has not yet been resolved and a screening strategy combining multiple methods can improve the accuracy and efficiency of drug screening. This study aimed to identify novel UT receptor agonists using a combination of docking-based, pharmacophore-based, and cell-based drug screening. First, the three-dimensional structures of the UT receptor were constructed through single-template, multi-template homologous modeling and threading strategies. After structure evaluation and ligand enrichment analysis, a model from the threading modeling was selected for docking-based virtual screening based on stepwise filtering, and 1368 positive compounds were obtained from our compound library. Second, the pharmacophore models were constructed using known ligands targeting the UT receptor for pharmacophore-based virtual screening. A model was selected after model validation, and 300 positive compounds were retrieved. Then, after intersecting the results of two different virtual screening methods with 570 compound entities from our primary screening, 14 compounds were obtained. Finally, three hits were obtained after in vitro confirmation. Furthermore, preliminary evaluation of the hits showed that they influenced glucose consumption. In summary, by integrating docking-based, pharmacophore-based, and in vitro drug screening, three new agonists targeting the UT receptor were identified which may serve as promising therapeutic agents for urotensinergic system disorders.

show abstract