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

Maria Elena Soto,Israel Pérez-Torres,Claudia Huesca,Xicoténcatl Vásquez,Giovanny Fuentevilla-Alvárez,Jorge A Díaz-Galindo,Vicente Castrejón-Tellez,Lináloe G Manzano-Pech,Verónica Guarner-Lans,Ricardo Gamboa

doi:10.1155/2020/5392454

Maria Elena Soto, Israel Pérez-Torres + Show 8 more

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https://doi.org/10.1155/2020/5392454

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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.

Highlights

The Loeys-Dietz syndrome (LDS) is a variant of the Marfan syndrome (MS), and in it, as in all complex genetic diseases, there is damage to different organs and systems
The antioxidant enzyme activities, including those of superoxide dismutase (SOD) isoforms, CAT, thioredoxin reductase (TrxR), and glutathione S-transferase (GST), decrease in the thoracic aortic aneurysms (TAA) of patients with LDS. These decreases in the enzyme activities favor the accumulation of reactive oxygen species (ROS) that contributes to GSH decrease and favor lipid peroxidation (LPO) and carbonylation
The glutathione reductase (GR) increase does not completely restore the GSH concentration, which is reflected in the decrease in the total antioxidant capacity (TAC) and in the enzymes that use it which contributes to and favors ROS production

Summary

Introduction

The Loeys-Dietz syndrome (LDS) is a variant of the Marfan syndrome (MS), and in it, as in all complex genetic diseases, there is damage to different organs and systems. Bart Loeys and Harry Dietz described the LDS in 2005 [1]. This syndrome is an autosomal dominant disease due to mutations in several genes including the gene that encodes for the beta. I receptor of transforming growth factor (TGF-βR1), which is located on chromosome 9q22.33; mutations in the TGFβR2 gene, located on chromosome 3p24.1; and mutations in the SMAD3 gene located on chromosome 15q22.33. The patients with LDS show complications during pregnancy, such as rupture of the uterus and death [2].

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