A study led by Dr. José Martínez-González, a researcher at Sant Pau Research Institute and the Biomedical Research Institute of Barcelona (IIBB-CSIC), and Dr. Cristina Rodríguez, head of the Cardiovascular Remodeling Regulatory Mechanisms group at IR Sant Pau, has identified lysyl oxidase (LOX) as a key component in cardiovascular calcification.
The study resulted from the collaboration of both researchers in the cardiovascular diseases field of the CIBER (CIBERCV) with researchers from CIBERCV at the Vall d’Hebron Hospital Research Institute (VHIR). Published in the Biomed Pharmacother journal, the research has demonstrated that the enzyme lysyl oxidase, which plays a fundamental role in determining the biomechanical properties of the extracellular matrix, has a significant role in the formation of mineral deposits in diseases such as aortic valve calcification and atherosclerosis.
“We have characterized how the alteration of the matrix induced by lysyl oxidase affects the development of valvular calcification, as well as the involvement of this enzyme in the development of atherosclerosis and calcification,” said Dr. Martínez-González.
The studies were conducted in two cohorts of patients with calcified aortic valve disease from Sant Pau Hospital and the University Hospital of Navarra. Analyses were performed on valve cells in culture and in an animal model that overexpresses human lysyl oxidase specifically in the vascular wall, inducing atherosclerosis and calcification. The research involved Dr. Antonio Rodríguez-Sinovas, a CIBERCV researcher at VHIR, and Dr. Natalia López-Andrés from NavarraBiomed.
“The results highlight the active contribution of lysyl oxidase in cardiovascular calcification and the importance of matrix remodeling, which acts as an anchor that promotes and guides the growth of calcium crystals in this disease,” explains Dr. Rodríguez.
“Cardiovascular calcification is a significant global health problem and an independent predictor of adverse cardiovascular events and mortality. Currently, there are no drugs available that can limit the development of this disease. This study suggests that treatment strategies targeting lysyl oxidase and matrix modification could be useful for its treatment,” concludes Dr. Carme Ballester, the first author of this work.
Carme Ballester-Servera, Judith Alonso, Laia Cañes, Paula Vázquez-Sufuentes, Lídia Puertas-Umbert, Amaya Fernández-Celis, Manel Taurón, Antonio Rodríguez-Sinovas, Natalia López-Andrés, Cristina Rodríguez, José Martínez-González, Lysyl oxidase-dependent extracellular matrix crosslinking modulates calcification in atherosclerosis and aortic valve disease, Biomedicine & Pharmacotherapy, Volume 167, 2023, 115469, ISSN 0753-3322, https://doi.org/10.1016/j.biopha.2023.115469.
