González Santamaría, JoséVillalba Orero, MaríaBusnadiego, OscarLópez Olañeta, MarinaSandoval, PilarSnabel, JessicaLópez Cabrera, ManuelErler, Janine T.Hanemaaijer, RoelandLara Pezzi, EnriqueRodríguez Pascual, Fernando2024-01-232024-01-232015-08-10González-Santamaría J, Villalba M, Busnadiego O, López-Olañeta MM, Sandoval P, Snabel J, López-Cabrera M, Erler JT, Hanemaaijer R, Lara-Pezzi E, Rodríguez-Pascual F. Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction. Cardiovasc Res. 2016 Jan 1;109(1):67-78. doi: 10.1093/cvr/cvv2140008-63631755-324510.1093/cvr/cvv214https://hdl.handle.net/20.500.14352/94738Aims: After myocardial infarction (MI), extensive remodelling of the extracellular matrix contributes to scar formation. While aiming to preserve tissue integrity, this fibrotic response is also associated with adverse events, including a markedly increased risk of heart failure, ventricular arrhythmias, and sudden cardiac death. Cardiac fibrosis is characterized by extensive deposition of collagen and also by increased stiffness as a consequence of enhanced collagen cross-linking. Members of the lysyl oxidase (LOX) family of enzymes are responsible for the formation of collagen cross-links. This study investigates the contribution of LOX family members to the heart response to MI. Methods and results: Experimental MI was induced in C57BL/6 mice by permanent ligation of the left anterior descending coronary artery. The expression of LOX isoforms (LOX and LOXL1-4) was strongly increased upon MI, and this response was accompanied by a significant accumulation of mature collagen fibres in the infarcted area. LOX expression was observed in areas of extensive remodelling, partially overlapping with α-smooth muscle actin-expressing myofibroblasts. Tumour growth factor-β as well as hypoxia-activated pathways contributed to the induction of LOX expression in cardiac fibroblasts. Finally, in vivo post-infarction treatment with the broadband LOX inhibitor β-aminopropionitrile or, selectively, with a neutralizing antibody against the canonical LOX isoform attenuated collagen accumulation and maturation and also resulted in reduced ventricular dilatation and improved cardiac function. Conclusion: LOX family members contribute significantly to the detrimental effects of cardiac remodelling, highlighting LOX inhibition as a potential therapeutic strategy for post-infarction recovery.engAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunctionjournal articlehttps://academic.oup.com/cardiovascres/article/109/1/67/246314526260798https://pubmed.ncbi.nlm.nih.gov/26260798/open access616.12Cardiac fibrosisCollagenLysyl oxidasesMyocardial infarctionMyofibroblastCiencias Biomédicas32 Ciencias Médicas