Abstract
Lysyl oxidase (LOX) proteins comprise a family of five copper-dependent enzymes (LOX and four LOX-like isoenzymes (LOXL1–4)) critical for extracellular matrix (ECM) homeostasis and remodeling. The primary role of LOX enzymes is to oxidize lysyl and hydroxylysyl residues from collagen and elastin chains into highly reactive aldehydes, which spontaneously react with surrounding amino groups and other aldehydes to form inter- and intra-catenary covalent cross-linkages. Therefore, they are essential for the synthesis of a mature ECM and assure matrix integrity. ECM modulates cellular phenotype and function, and strikingly influences the mechanical properties of tissues. This explains the critical role of these enzymes in tissue homeostasis, and in tissue repair and remodeling. Cardiac ECM is mainly composed of fibrillar collagens which form a complex network that provides structural and biochemical support to cardiac cells and regulates cell signaling pathways. It is now becoming apparent that cardiac performance is affected by the structure and composition of the ECM and that any disturbance of the ECM contributes to cardiac disease progression. This review article compiles the major findings on the contribution of the LOX family to the development and progression of myocardial disorders.
Highlights
Lysyl oxidase (LOX) proteins comprise a family of copper-dependent enzymes which governs extracellular matrix (ECM) homeostasis and remodeling
The findings summarized in this review evidence the critical contribution of the LOX family to cardiac function and remodeling
The upregulation of LOX/LOX-like isoenzymes (LOXLs) seems to be a feature of several fibrotic processes affecting the heart, from those associated to post-myocardial infarction (MI) cardiac remodeling, cardiac hypertrophy triggered by pressure or volume overload, heart failure with preserved ejectionejection fraction (HFPEF) associated with obesity and metabolic syndrome or Atrial fibrillation (AF)
Summary
Lysyl oxidase (LOX) proteins comprise a family of copper-dependent enzymes which governs extracellular matrix (ECM) homeostasis and remodeling. Dependent enzymes: LOX and four LOX-like isoenzymes This proteolytic processing releases the catalytically active forms Beyond ECM cross-linking, additional biological functions have been reported for LOX and LOXLs (LOX/LOXLs) [1,2,3], including the control of cell adhesion migration and proliferation and the modulation of gene transcription and epithelial to-mesenchymal transition. Active intracellular forms (both cytoplasmic and nuclear) for LOX/LOXLs have been described [18,19,20], while the pro-peptide (LOX-PP) released during the proteolytic processing of LOX exhibits biological activity [2,21] (Figure 3).
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