Impact of Oxidative Stress and Protein S-Glutathionylation in Aortic Valve Sclerosis Patients with Overt Atherosclerosis
AbstractAortic 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
- Supplementary File 1:
PDF-Document (PDF, 413 KB)
Share & Cite This Article
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.
Valerio V, Myasoedova VA, Moschetta D, Porro B, Perrucci GL, Cavalca V, Cavallotti L, Songia P, Poggio P. Impact of Oxidative Stress and Protein S-Glutathionylation in Aortic Valve Sclerosis Patients with Overt Atherosclerosis. Journal of Clinical Medicine. 2019; 8(4):552.Chicago/Turabian Style
Valerio, Vincenza; Myasoedova, Veronika A.; Moschetta, Donato; Porro, Benedetta; Perrucci, Gianluca L.; Cavalca, Viviana; Cavallotti, Laura; Songia, Paola; Poggio, Paolo. 2019. "Impact of Oxidative Stress and Protein S-Glutathionylation in Aortic Valve Sclerosis Patients with Overt Atherosclerosis." J. Clin. Med. 8, no. 4: 552.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.