Next Article in Journal
Analgesic Effect of Low Dose Nefopam Hydrochloride after Arthroscopic Rotator Cuff Repair: A Randomized Controlled Trial
Previous Article in Journal
Global Burden Related to Nitrous Oxide Exposure in Medical and Recreational Settings: A Systematic Review and Individual Patient Data Meta-Analysis
Article Menu
Issue 4 (April) cover image

Export Article

Open AccessArticle

Impact of Oxidative Stress and Protein S-Glutathionylation in Aortic Valve Sclerosis Patients with Overt Atherosclerosis

1
Centro Cardiologico Monzino IRCCS, Unit for the Study of Aortic, Valvular and Coronary Pathologies, 20138 Milan, Italy
2
Università degli Studi di Napoli Federico II, Dipartimento di Medicina Clinica e Chirurgia, 80131 Napoli, Italy
3
Centro Cardiologico Monzino IRCCS, Unit of Metabolomics and Cellular Biochemistry of Atherothrombosis, 20138 Milan, Italy
4
Centro Cardiologico Monzino IRCCS, Unit of Vascular Biology and Regenerative Medicine, 20138 Milan, Italy
5
Centro Cardiologico Monzino IRCCS, Cardiac Surgery Unit, 20138 Milan, Italy
*
Author to whom correspondence should be addressed.
These authors equally contributed.
J. Clin. Med. 2019, 8(4), 552; https://doi.org/10.3390/jcm8040552
Received: 27 March 2019 / Revised: 16 April 2019 / Accepted: 18 April 2019 / Published: 24 April 2019
(This article belongs to the Section Vascular Medicine)
  |  
PDF [1979 KB, uploaded 24 April 2019]
  |  

Abstract

Aortic valve sclerosis (AVSc) is characterized by non-uniform thickening of the leaflets without hemodynamic changes. Endothelial dysfunction, also caused by dysregulation of glutathione homeostasis expressed as ratio between its reduced (GSH) and its oxidised form (GSSG), could represent one of the pathogenic triggers of AVSc. We prospectively enrolled 58 patients with overt atherosclerosis and requiring coronary artery bypass grafting (CABG). The incidence of AVSc in the studied population was 50%. The two groups (No-AVSc and AVSc) had similar clinical characteristics. Pre-operatively, AVSc group showed significantly lower GSH/GSSG ratio than No-AVSc group (p = 0.02). Asymmetric dimethylarginine (ADMA) concentration was significantly higher in AVSc patients compared to No-AVSc patients (p < 0.0001). Explanted sclerotic aortic valves presented a significantly increased protein glutathionylation (Pr-SSG) than No-AVSc ones (p = 0.01). In vitro, inhibition of glutathione reductase caused β-actin glutathionylation, activation of histone 2AX, upregulation of α2 smooth muscle actin (ACTA2), downregulation of platelet and endothelial cell adhesion molecule 1 (PECAM1) and cadherin 5 (CDH5). In this study, we showed for the first time that the dysregulation of glutathione homeostasis is associated with AVSc. We found that Pr-SSG is increased in AVSc leaflets and it could lead to EndMT via DNA damage. Further studies are warranted to elucidate the causal role of Pr-SSG in aortic valve degeneration. View Full-Text
Keywords: calcific aortic valve disease; coronary artery disease; glutathione homeostasis; endothelial cells; endothelial to mesenchymal transition calcific aortic valve disease; coronary artery disease; glutathione homeostasis; endothelial cells; endothelial to mesenchymal transition
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Supplementary material

SciFeed

Share & Cite This Article

MDPI and ACS Style

Valerio, V.; Myasoedova, V.A.; Moschetta, D.; Porro, B.; Perrucci, G.L.; Cavalca, V.; Cavallotti, L.; Songia, P.; Poggio, P. Impact of Oxidative Stress and Protein S-Glutathionylation in Aortic Valve Sclerosis Patients with Overt Atherosclerosis. J. Clin. Med. 2019, 8, 552.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
J. Clin. Med. EISSN 2077-0383 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top