2026-06-14T03:28:59Zhttps://repisalud.isciii.es/rest/oai/request

oai:repisalud.isciii.es:20.500.12105/79852024-09-27T09:24:23Zcom_20.500.12105_19604com_20.500.12105_2051col_20.500.12105_19605

00925njm 22002777a 4500 dc González-Santamaría, José author Villalba, María author Busnadiego, Oscar author Lopez-Olaneta, Marina author Sandoval, Pilar author Snabel, Jessica author López-Cabrera, Manuel author Erler, Janine T author Hanemaaijer, Roeland author Lara-Pezzi, Enrique author Rodríguez-Pascual, Fernando author 2016-01 AIMS: 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. Cardiovasc Res. 2016; 109(1):67-78 10.1093/cvr/cvv214 1755-3245 0008-6363 Cardiovascular research 26260798 http://hdl.handle.net/20.500.12105/7985 Cardiac fibrosis Collagen Lysyl oxidases Myocardial infarction Myofibroblast Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction