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Role of the lysyl oxidase enzyme family in cardiac function and disease.
- Source :
-
Cardiovascular research [Cardiovasc Res] 2019 Nov 01; Vol. 115 (13), pp. 1820-1837. - Publication Year :
- 2019
-
Abstract
- Heart diseases are a major cause of morbidity and mortality world-wide. Lysyl oxidase (LOX) and related LOX-like (LOXL) isoforms play a vital role in remodelling the extracellular matrix (ECM). The LOX family controls ECM formation by cross-linking collagen and elastin chains. LOX/LOXL proteins are copper-dependent amine oxidases that catalyse the oxidation of lysine, causing cross-linking between the lysine moieties of lysine-rich proteins. Dynamic changes in LOX and LOXL protein-expression occur in a variety of cardiac pathologies; these changes are believed to be central to the associated tissue-fibrosis. An awareness of the potential pathophysiological importance of LOX has led to the evaluation of interventions that target LOX/LOXL proteins for heart-disease therapy. The purposes of this review article are: (i) to summarize the basic biochemistry and enzyme function of LOX and LOXL proteins; (ii) to consider their tissue and species distribution; and (iii) to review the results of experimental studies of the roles of LOX and LOXL proteins in heart disease, addressing involvement in the mechanisms, pathophysiology and therapeutic responses based on observations in patient samples and relevant animal models. Therapeutic targeting of LOX family enzymes has shown promising results in animal models, but small-molecule approaches have been limited by non-specificity and off-target effects. Biological approaches show potential promise but are in their infancy. While there is strong evidence for LOX-family protein participation in heart failure, myocardial infarction, cardiac hypertrophy, dilated cardiomyopathy, atrial fibrillation and hypertension, as well as potential interest as therapeutic targets, the precise involvement of LOX-family proteins in heart disease requires further investigation.<br /> (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)
- Subjects :
- Animals
Extracellular Matrix pathology
Fibrosis
Gene Expression Regulation, Enzymologic
Heart Diseases genetics
Heart Diseases pathology
Heart Diseases physiopathology
Humans
Protein Conformation
Protein-Lysine 6-Oxidase chemistry
Protein-Lysine 6-Oxidase genetics
Signal Transduction
Structure-Activity Relationship
Extracellular Matrix enzymology
Heart Diseases enzymology
Myocardium enzymology
Protein-Lysine 6-Oxidase metabolism
Ventricular Remodeling
Subjects
Details
- Language :
- English
- ISSN :
- 1755-3245
- Volume :
- 115
- Issue :
- 13
- Database :
- MEDLINE
- Journal :
- Cardiovascular research
- Publication Type :
- Academic Journal
- Accession number :
- 31504232
- Full Text :
- https://doi.org/10.1093/cvr/cvz176