Emerging Roles of Lysyl Oxidases in the Cardiovascular System: New Concepts and Therapeutic Challenges
1
Instituto de Investigaciones Biomédicas de Barcelona (IIBB-CSIC), 08036 Barcelona, Spain
2
CIBER de Enfermedades Cardiovasculares, Instituto de Salud Carlos III, 28029 Madrid, Spain
3
Instituto de Investigación Biomédica Sant Pau (IIB-Sant Pau), 08041 Barcelona, Spain
4
Institut de Recerca Hospital de la Santa Creu i Sant Pau-Programa ICCC, 08025 Barcelona, Spain
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Departmento de Farmacología, Facultad de Medicina, Universidad Autónoma de Madrid, Instituto de Investigación Hospital La Paz, 28029 Madrid, Spain
6
Departamento de Fisiología, Facultad de Medicina, Universidad Complutense de Madrid-Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), 28040 Madrid, Spain
*
Author to whom correspondence should be addressed.
Biomolecules 2019, 9(10), 610; https://doi.org/10.3390/biom9100610
Received: 16 September 2019 / Revised: 7 October 2019 / Accepted: 10 October 2019 / Published: 14 October 2019
(This article belongs to the Special Issue Lysyl Oxidases: Novel Roles in Disease and Therapeutic Opportunities)
Lysyl oxidases (LOX and LOX-likes (LOXLs) isoenzymes) belong to a family of copper-dependent enzymes classically involved in the covalent cross-linking of collagen and elastin, a pivotal process that ensures extracellular matrix (ECM) stability and provides the tensile and elastic characteristics of connective tissues. Besides this structural role, in the last years, novel biological properties have been attributed to these enzymes, which can critically influence cardiovascular function. LOX and LOXLs control cell proliferation, migration, adhesion, differentiation, oxidative stress, and transcriptional regulation and, thereby, their dysregulation has been linked to a myriad of cardiovascular pathologies. Lysyl oxidase could modulate virtually all stages of the atherosclerotic process, from endothelial dysfunction and plaque progression to calcification and rupture of advanced and complicated plaques, and contributes to vascular stiffness in hypertension. The alteration of LOX/LOXLs expression underlies the development of other vascular pathologies characterized by a destructive remodeling of the ECM, such as aneurysm and artery dissections, and contributes to the adverse myocardial remodeling and dysfunction in hypertension, myocardial infarction, and obesity. This review examines the most recent advances in the study of LOX and LOXLs biology and their pathophysiological role in cardiovascular diseases with special emphasis on their potential as therapeutic targets.
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Keywords:
lysyl oxidases; cardiovascular diseases; atherosclerosis; aortic aneurysm; vascular calcification; vascular stiffness; myocardial fibrosis
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MDPI and ACS Style
Martínez-González, J.; Varona, S.; Cañes, L.; Galán, M.; Briones, A.M; Cachofeiro, V.; Rodríguez, C. Emerging Roles of Lysyl Oxidases in the Cardiovascular System: New Concepts and Therapeutic Challenges. Biomolecules 2019, 9, 610.
AMA Style
Martínez-González J, Varona S, Cañes L, Galán M, Briones AM, Cachofeiro V, Rodríguez C. Emerging Roles of Lysyl Oxidases in the Cardiovascular System: New Concepts and Therapeutic Challenges. Biomolecules. 2019; 9(10):610.
Chicago/Turabian StyleMartínez-González, José; Varona, Saray; Cañes, Laia; Galán, María; Briones, Ana M; Cachofeiro, Victoria; Rodríguez, Cristina. 2019. "Emerging Roles of Lysyl Oxidases in the Cardiovascular System: New Concepts and Therapeutic Challenges" Biomolecules 9, no. 10: 610.
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