Redox Metabolism and Vascular Calcification in Chronic Kidney Disease

• Published in: Biomolecules (Basel, Switzerland) Switzerland), 2023-09, Vol.13 (9), p.1419
• Main Authors: Carrillo-López, Natalia, Panizo, Sara, Martín-Carro, Beatriz, Mayo Barrallo, Juan Carlos, Román-García, Pablo, García-Castro, Raúl, Fernández-Gómez, Jesús María, Hevia-Suárez, Miguel Ángel, Martín-Vírgala, Julia, Fernández-Villabrille, Sara, Martínez-Arias, Laura, Vázquez, Sara Barrio, Calleros Basilio, Laura, Naves-Díaz, Manuel, Cannata-Andía, Jorge Benito, Quirós-González, Isabel, Alonso-Montes, Cristina, Fernández-Martín, José Luis
• Format: Article
• Language: English
• Subjects: Antibodies; Antioxidants; Aorta; Arteries; Blood circulation disorders; Calcification; Calcification (ectopic); Catalase; Causes of; Cbfa-1 protein; Cell metabolism; Chronic kidney failure; CKD; Complications and side effects; Coronary vessels; Cytoplasm; Development and progression; DIGE; Enzymes; epigastric arteries; Glutathione peroxidase; Health aspects; Homeostasis; Hydrogen peroxide; Kidney diseases; Kidney transplantation; Kidney transplants; Laboratory animals; Metabolism; Metabolites; Oxidation-reduction reaction; Oxidative stress; Phosphorus; Proteins; Redox properties; Risk factors; RUNX2; Smooth muscle; vascular calcification; Veins & arteries
• ISSN: 2218-273X; 2218-273X
• DOI: 10.3390/biom13091419

Vascular calcification (VC) is a common complication in patients with chronic kidney disease which increases their mortality. Although oxidative stress is involved in the onset and progression of this disorder, the specific role of some of the main redox regulators, such as catalase, the main scavenger of H2O2, remains unclear. In the present study, epigastric arteries of kidney transplant recipients, a rat model of VC, and an in vitro model of VC exhibiting catalase (Cts) overexpression were analysed. Pericalcified areas of human epigastric arteries had increased levels of catalase and cytoplasmic, rather than nuclear runt-related transcription factor 2 (RUNX2). In the rat model, advanced aortic VC concurred with lower levels of the H2O2-scavenger glutathione peroxidase 3 compared to controls. In an early model of calcification using vascular smooth muscle cells (VSMCs), Cts VSMCs showed the expected increase in total levels of RUNX2. However, Cts VMSCs also exhibited a lower percentage of the nucleus stained for RUNX2 in response to calcifying media. In this early model of VC, we did not observe a dysregulation of the mitochondrial redox state; instead, an increase in the general redox state was observed in the cytoplasm. These results highlight the complex role of antioxidant enzymes as catalase by regulation of RUNX2 subcellular location delaying the onset of VC.