دورية أكاديمية
أعرض في EDS

Hydrogen sulfide dysfunction in metabolic syndrome-associated vascular complications involves cGMP regulation through soluble guanylyl cyclase persulfidation.

التفاصيل البيبلوغرافية
العنوان: Hydrogen sulfide dysfunction in metabolic syndrome-associated vascular complications involves cGMP regulation through soluble guanylyl cyclase persulfidation.
المؤلفون: Smimmo M; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy., Casale V; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy., Casillo GM; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy., Mitidieri E; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy., d'Emmanuele di Villa Bianca R; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy., Bello I; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy., Schettino A; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy., Montanaro R; Department of Science, University of Basilicata, Potenza, Italy., Brancaleone V; Department of Science, University of Basilicata, Potenza, Italy., Indolfi C; Department of Molecular Medicine and Medical Biotechnology, School of Medicine and Surgery, University of Naples Federico II, Naples 80131, Italy., Cirino G; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy., Di Lorenzo A; Department of Pathology and Laboratory Medicine Center for Vascular Biology, Weill Cornell Medical College, Cornell University, New York, USA., Bucci M; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy. Electronic address: mrbucci@unina.it., Panza E; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy., Vellecco V; Department of Pharmacy, School of Medicine and Surgery, University of Naples Federico II, Naples, Italy.
المصدر: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie [Biomed Pharmacother] 2024 May; Vol. 174, pp. 116466. Date of Electronic Publication: 2024 Mar 28.
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: Editions Scientifiques Elsevier Country of Publication: France NLM ID: 8213295 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1950-6007 (Electronic) Linking ISSN: 07533322 NLM ISO Abbreviation: Biomed Pharmacother Subsets: MEDLINE
أسماء مطبوعة: Publication: Paris : Editions Scientifiques Elsevier
Original Publication: New York, N.Y. : Masson Pub. USA, Inc., c1982-
مواضيع طبية MeSH: Hydrogen Sulfide*/metabolism , Hydrogen Sulfide*/pharmacology , Cyclic GMP*/metabolism , Metabolic Syndrome*/metabolism , Soluble Guanylyl Cyclase*/metabolism , Mice, Inbred C57BL*, Animals ; Mice ; Male ; Vasodilation/drug effects ; Signal Transduction/drug effects ; Nitric Oxide Synthase Type III/metabolism ; Humans ; Endothelium, Vascular/drug effects ; Endothelium, Vascular/metabolism ; Nitric Oxide/metabolism ; Aorta/drug effects ; Aorta/metabolism ; Vascular Diseases/metabolism ; Disease Models, Animal
مستخلص: Here, by using in vitro and ex vivo approaches, we elucidate the impairment of the hydrogen sulfide (H 2 S) pathway in vascular complications associated with metabolic syndrome (MetS). In the in vitro model simulating hyperlipidemic/hyperglycemic conditions, we observe significant hallmarks of endothelial dysfunction, including eNOS/NO signaling impairment, ROS overproduction, and a reduction in CSE-derived H 2 S. Transitioning to an ex vivo model using db/db mice, a genetic MetS model, we identify a downregulation of CBS and CSE expression in aorta, coupled with a diminished L-cysteine-induced vasorelaxation. Molecular mechanisms of eNOS/NO signaling impairment, dissected using pharmacological and molecular approaches, indicate an altered eNOS/Cav-1 ratio, along with reduced Ach- and Iso-induced vasorelaxation and increased L-NIO-induced contraction. In vivo treatment with the H 2 S donor Erucin ameliorates vascular dysfunction observed in db/db mice without impacting eNOS, further highlighting a specific action on smooth muscle component rather than the endothelium. Analyzing the NO signaling pathway in db/db mice aortas, reduced cGMP levels were detected, implicating a defective sGC/cGMP signaling. In vivo Erucin administration restores cGMP content. This beneficial effect involves an increased sGC activity, due to enzyme persulfidation observed in sGC overexpressed cells, coupled with PDE5 inhibition. In conclusion, our study demonstrates a pivotal role of reduced cGMP levels in impaired vasorelaxation in a murine model of MetS involving an impairment of both H 2 S and NO signaling. Exogenous H 2 S supplementation through Erucin represents a promising alternative in MetS therapy, targeting smooth muscle cells and supporting the importance of lifestyle and nutrition in managing MetS.
Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest.
(Copyright © 2024 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)
فهرسة مساهمة: Keywords: H(2)S donors; aorta; db/db mice; metabolic syndrome; soluble guanylyl cyclase
المشرفين على المادة: YY9FVM7NSN (Hydrogen Sulfide)
H2D2X058MU (Cyclic GMP)
EC 4.6.1.2 (Soluble Guanylyl Cyclase)
EC 1.14.13.39 (Nitric Oxide Synthase Type III)
31C4KY9ESH (Nitric Oxide)
تواريخ الأحداث: Date Created: 20240329 Date Completed: 20240430 Latest Revision: 20240502
رمز التحديث: 20240502
DOI: 10.1016/j.biopha.2024.116466
PMID: 38552439
قاعدة البيانات: MEDLINE
الوصف
تدمد:1950-6007
DOI:10.1016/j.biopha.2024.116466