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Matrix cross-linking lysyl oxidases are induced in response to myocardial infarction and promote cardiac dysfunction.
- Source :
-
Cardiovascular Research . Jan2016, Vol. 109 Issue 1, p67-78. 12p. 1 Color Photograph, 4 Charts, 5 Graphs. - Publication Year :
- 2016
-
Abstract
- 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. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00086363
- Volume :
- 109
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Cardiovascular Research
- Publication Type :
- Academic Journal
- Accession number :
- 112045796
- Full Text :
- https://doi.org/10.1093/cvr/cvv214