2024-03-19T09:33:52Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/79852022-10-25T11:25:07Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
Repisalud
author
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
funder
Ministerio de Economía y Competitividad (España)
funder
Comunidad de Madrid (España)
funder
Unión Europea. Comisión Europea
2019-07-29T14:48:47Z
2019-07-29T14:48:47Z
2016-01
Cardiovasc Res. 2016; 109(1):67-78
0008-6363
http://hdl.handle.net/20.500.12105/7985
26260798
10.1093/cvr/cvv214
1755-3245
Cardiovascular research
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.
eng
Cardiac fibrosis
Collagen
Lysyl oxidases
Myocardial infarction
Myofibroblast
Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction
journal article
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URL
https://repisalud.isciii.es/bitstream/20.500.12105/7985/1/MatrixCrossLinkingLysyl_2016.pdf
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MatrixCrossLinkingLysyl_2016.pdf
URL
https://repisalud.isciii.es/bitstream/20.500.12105/7985/3/MatrixCrossLinkingLysyl_2016.pdf.txt
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MatrixCrossLinkingLysyl_2016.pdf.txt