Dataset Information

Global Oxidative Status Is Linked to Calcific Aortic Stenosis: The Differences Due to Diabetes Mellitus and the Effects of Metformin.

ABSTRACT: Calcific aortic stenosis (CAS) and type 2 diabetes mellitus (T2DM) are related and often concomitant pathologies, accompanied by common comorbidities such as hypertension or dyslipidemia. Oxidative stress is one of the mechanisms that trigger CAS, and it can drive the vascular complications in T2DM. Metformin can inhibit oxidative stress, yet its effects have not been studied in the context of CAS. Here, we assessed the global oxidative status in plasma from patients with CAS, both alone and with T2DM (and under treatment with metformin), using multimarker scores of systemic oxidative damage (OxyScore) and antioxidant defense (AntioxyScore). The OxyScore was determined by measuring carbonyls, oxidized LDL (oxLDL), 8-hydroxy-20-deoxyguanosine (8-OHdG), and xanthine oxidase (XOD) activity. In contrast, the AntioxyScore was determined through the catalase (CAT) and superoxide dismutase (SOD) activity, as well as the total antioxidant capacity (TAC). Patients with CAS displayed enhanced oxidative stress compared to control subjects, probably exceeding their antioxidant capacity. Interestingly, patients with CAS and T2DM displayed less oxidative stress, possibly due to the benefits of their pharmacological therapy (metformin). Thus, reducing oxidative stress or enhancing antioxidant capacity through specific therapies could be a good strategy to manage CAS, focusing on personalized medicine.

SUBMITTER: Corbacho-Alonso N

PROVIDER: S-EPMC10215415 | biostudies-literature | 2023 Apr

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Global Oxidative Status Is Linked to Calcific Aortic Stenosis: The Differences Due to Diabetes Mellitus and the Effects of Metformin.

Corbacho-Alonso Nerea N Rodríguez-Sánchez Elena E Sastre-Oliva Tamara T Mercado-García Elisa E Perales-Sánchez Ines I Juarez-Alia Cristina C López-Almodovar Luis F LF Padial Luis R LR Tejerina Teresa T Mourino-Alvarez Laura L Ruiz-Hurtado Gema G Barderas María G MG

Antioxidants (Basel, Switzerland) 20230428 5

Calcific aortic stenosis (CAS) and type 2 diabetes mellitus (T2DM) are related and often concomitant pathologies, accompanied by common comorbidities such as hypertension or dyslipidemia. Oxidative stress is one of the mechanisms that trigger CAS, and it can drive the vascular complications in T2DM. Metformin can inhibit oxidative stress, yet its effects have not been studied in the context of CAS. Here, we assessed the global oxidative status in plasma from patients with CAS, both alone and wit ...[more]

PMID: 37237890

Similar Datasets

Project description:The aim of this study was to determine whether oxidative stress is increased in calcified, stenotic aortic valves and to examine mechanisms that might contribute to increased oxidative stress.Oxidative stress is increased in atherosclerotic lesions and might play an important role in plaque progression and calcification. The role of oxidative stress in valve disease is not clear.Superoxide (dihydroethidium fluorescence and lucigenin-enhanced chemiluminescence), hydrogen peroxide H2O2 (dichlorofluorescein fluorescence), and expression and activity of pro- and anti-oxidant enzymes were measured in normal valves from hearts not suitable for transplantation and stenotic aortic valves that were removed during surgical replacement of the valve.In normal valves, superoxide levels were relatively low and distributed homogeneously throughout the valve. In stenotic valves, superoxide levels were increased 2-fold near the calcified regions of the valve (p < 0.05); noncalcified regions did not differ significantly from normal valves. Hydrogen peroxide levels were also markedly elevated in calcified regions of stenotic valves. Nicotinamide adenine dinucleotide phosphate oxidase activity was not increased in calcified regions of stenotic valves. Superoxide levels in stenotic valves were significantly reduced by inhibition of nitric oxide synthases (NOS), which suggests uncoupling of the enzyme. Antioxidant mechanisms were reduced in calcified regions of the aortic valve, because total superoxide dismutase (SOD) activity and expression of all 3 SOD isoforms was significantly decreased. Catalase expression also was reduced in pericalcific regions.This study provides the first evidence that oxidative stress is increased in calcified regions of stenotic aortic valves from humans. Increased oxidative stress is due at least in part to reduction in expression and activity of antioxidant enzymes and perhaps to uncoupled NOS activity. Thus, mechanisms of oxidative stress differ greatly between stenotic aortic valves and atherosclerotic arteries.

Dataset Information

Global Oxidative Status Is Linked to Calcific Aortic Stenosis: The Differences Due to Diabetes Mellitus and the Effects of Metformin.

Publications

Global Oxidative Status Is Linked to Calcific Aortic Stenosis: The Differences Due to Diabetes Mellitus and the Effects of Metformin.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets