Oxidant/Antioxidant Profile in the Thoracic Aneurysm of Patients with the Loeys-Dietz Syndrome

Abstract

Patients with the Loeys-Dietz syndrome (LDS) have mutations in the TGF-βR1, TGF-βR2, and SMAD3 genes. However, little is known about the redox homeostasis in the thoracic aortic aneurysms (TAA) they develop. Here, we evaluate the oxidant/antioxidant profile in the TAA tissue from LDS patients and compare it with that in nondamaged aortic tissue from control (C) subjects. We evaluate the enzymatic activities of glutathione peroxidase (GPx), glutathione S-transferase (GST), glutathione reductase (GR), catalase (CAT), superoxide dismutase (SOD) isoforms, and thioredoxin reductase (TrxR). We also analyze some antioxidants from a nonenzymatic system such as selenium (Se), glutathione (GSH), and total antioxidant capacity (TAC). Oxidative stress markers such as lipid peroxidation and carbonylation, as well as xanthine oxidase (ORX) and nuclear factor erythroid 2-related factor 2 (Nrf2) expressions, were also evaluated. TAA from LDS patients showed a decrease in GSH, Se, TAC, GPx, GST, CAT, and TrxR. The SOD activity and ORX expressions were increased, but the Nrf2 expression was decreased. The results suggest that the redox homeostasis is altered in the TAA from LDS patients, favoring ROS overproduction that contributes to the decrease in GSH and TAC and leads to LPO and carbonylation. The decrease in Se and Nrf2 alters the activity and/or expression of some antioxidant enzymes, thus favoring a positive feedback oxidative background that contributes to the TAA formation.

Usefulness of Antioxidants as Adjuvant Therapy for Septic Shock: A Randomized Clinical Trial

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Reactive Oxygen Species and Oxidative Stress in the Pathogenesis and Progression of Genetic Diseases of the Connective Tissue

“…Nevertheless, a couple of recent studies provide evidence of their involvement. In a similar study previously carried out in MFS patients, the content of enzymatic and nonenzymatic systems involved in redox stress was measured in plasma and TAA from LDS patients [ 268 ]. This group observed a significant reduction of antioxidative stress mechanisms (GSH, antioxidant capacity, glutathione peroxidase, glutathione-S-transferase, catalase, and thioredoxin reductase) accompanied by an increase in both SOD and XO activities.…”