-
Tytuł:
-
l-Arginine prevents inflammatory and pro-calcific differentiation of interstitial aortic valve cells.
-
Autorzy:
-
Rattazzi M; Department of Medicine, University of Padova, Italy; Medicina Interna I^, Cà Foncello Hospital, Treviso, Italy. Electronic address: .
Donato M; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Italy.
Bertacco E; Department of Medicine, University of Padova, Italy.
Millioni R; Department of Medicine, University of Padova, Italy; Proteomics Center, University of Padova and Azienda Ospedaliera di Padova, Italy.
Franchin C; Department of Biomedical Sciences, University of Padova, Italy; Proteomics Center, University of Padova and Azienda Ospedaliera di Padova, Italy.
Mortarino C; Department of Statistical Sciences, University of Padova, Italy.
Faggin E; Department of Medicine, University of Padova, Italy.
Nardin C; Department of Medicine, University of Padova, Italy; Medicina Interna I^, Cà Foncello Hospital, Treviso, Italy.
Scarpa R; Department of Medicine, University of Padova, Italy; Medicina Interna I^, Cà Foncello Hospital, Treviso, Italy.
Cinetto F; Department of Medicine, University of Padova, Italy; Medicina Interna I^, Cà Foncello Hospital, Treviso, Italy.
Agostini C; Department of Medicine, University of Padova, Italy; Medicina Interna I^, Cà Foncello Hospital, Treviso, Italy.
Ferri N; Department of Pharmaceutical and Pharmacological Sciences, University of Padova, Italy.
Pauletto P; ORAS Rehabilitation Hospital, Motta di Livenza, Treviso, Italy.
Arrigoni G; Department of Biomedical Sciences, University of Padova, Italy; Proteomics Center, University of Padova and Azienda Ospedaliera di Padova, Italy.
-
Źródło:
-
Atherosclerosis [Atherosclerosis] 2020 Apr; Vol. 298, pp. 27-35. Date of Electronic Publication: 2020 Mar 05.
-
Typ publikacji:
-
Journal Article; Research Support, Non-U.S. Gov't
-
Język:
-
English
-
Imprint Name(s):
-
Publication: Limerick : Elsevier
Original Publication: Amsterdam, Elsevier.
-
MeSH Terms:
-
Aortic Valve/*drug effects
Aortic Valve/*pathology
Aortic Valve Stenosis/*metabolism
Arginine/*metabolism
Arginine/*pharmacology
Arteritis/*metabolism
Calcinosis/*metabolism
Alkaline Phosphatase/antagonists & inhibitors ; Alkaline Phosphatase/metabolism ; Animals ; Aortic Valve/cytology ; Aortic Valve/metabolism ; Cattle ; Cell Differentiation/drug effects ; Cells, Cultured ; Osteogenesis/drug effects ; Proteomics
-
Contributed Indexing:
-
Keywords: Aortic valve calcification; Inflammation; L-Arginine; Nitric oxide; Proteomics
-
Substance Nomenclature:
-
94ZLA3W45F (Arginine)
EC 3.1.3.1 (Alkaline Phosphatase)
-
SCR Disease Name:
-
Aortic Valve, Calcification of
-
Entry Date(s):
-
Date Created: 20200315 Date Completed: 20210129 Latest Revision: 20210129
-
Update Code:
-
20240105
-
DOI:
-
10.1016/j.atherosclerosis.2020.02.024
-
PMID:
-
32169720
-
Background and Aims: Reduced bioavailability of nitric oxide (NO) has been implicated in the pathogenesis of calcific aortic stenosis. Herein, we investigated the effects of l-Arginine, the main precursor of NO, on the osteogenic differentiation of aortic interstitial valve cells (VICs).
Methods: We isolated a clonal population of bovine VICs that expresses osteogenic markers and induces calcification of collagen matrix after stimulation with endotoxin (LPS 500 ng/mL). VICs were treated in vitro with different combinations of LPS ± l-Arginine (50 or 100 mM) and cell extracts were collected to perform proteomic (iTRAQ) and gene expression (RT-PCR) analysis.
Results: l-Arginine prevents the over-expression of alkaline phosphatase (ALP, p < 0.001) and reduces matrix calcification (p < 0.05) in VICs treated with LPS. l-Arginine also reduces the over-expression of inflammatory molecules induced by LPS (TNF-alpha, IL-6 and IL-1beta, p < 0.001). The proteomic analysis allowed to identify 49 proteins with an altered expression profile after stimulation with LPS and significantly modified by l-Arginine. These include proteins involved in the redox homeostasis of the cells (i.e. Xanthine Oxidase, Catalase, Aldehyde Oxidase), remodeling of the extracellular matrix (i.e. ADAMTSL4, Basigin, COL3A1) and cellular signaling (i.e. Fibrillin-1, Legumain, S100A13). The RT-PCR analysis confirmed the modifications of Fibrillin-1, ADAMTSL4, Basigin and Xanthine Oxidase, whose expression levels increase after stimulation with LPS and are reduced by l-Arginine (p < 0.05).
Conclusions: l-Arginine prevents osteogenic differentiation of VICs and reduces matrix calcification. This effect is achieved through the modulation of proteins involved in the cellular redox system, remodeling of extracellular matrix and inflammatory activation of VICs.
Competing Interests: Declaration of competing interest The authors declared they do not have anything to disclose regarding conflict of interest with respect to this manuscript.
(Copyright © 2020 Elsevier B.V. All rights reserved.)
