Inhibitor of lysyl oxidase improves cardiac function and the collagen/MMP profile in response to volume overload

American Journal of Physiology. Heart and Circulatory Physiology
Elia C El HajjJason D Gardner

Abstract

The cardiac extracellular matrix is a complex architectural network that serves many functions, including providing structural and biochemical support to surrounding cells and regulating intercellular signaling pathways. Cardiac function is directly affected by extracellular matrix (ECM) composition, and alterations of the ECM contribute to the progression of heart failure. Initially, collagen deposition is an adaptive response that aims to preserve tissue integrity and maintain normal ventricular function. However, the synergistic effects of proinflammatory and profibrotic responses induce a vicious cycle, which causes excess activation of myofibroblasts, significantly increasing collagen deposition and accumulation in the matrix. Furthermore, excess synthesis and activation of the enzyme lysyl oxidase (LOX) during disease increases collagen cross-linking, which significantly increases collagen resistance to degradation by matrix metalloproteinases (MMPs). In the present study, the aortocaval fistula model of volume overload (VO) was used to determine whether LOX inhibition could prevent adverse changes in the ECM and subsequent cardiac dysfunction. The major findings from this study were that LOX inhibition 1) prevented VO-in...Continue Reading

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Citations

Jun 2, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Sayantan Jana, Zamaneh Kassiri
Sep 22, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Maria BloksgaardLuis A Martinez-Lemus
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Sep 11, 2019·Cardiovascular Research·Doa'a Al-U'dattStanley Nattel
Apr 9, 2020·Frontiers in Cell and Developmental Biology·Lijun ZhaoFang Liu
Mar 29, 2020·American Journal of Physiology. Heart and Circulatory Physiology·Leslie M OgilvieJeremy A Simpson
Aug 9, 2019·Biochimica Et Biophysica Acta. Molecular Cell Research·Arantxa GonzálezJavier Díez
Feb 12, 2021·Nature Reviews. Cardiology·Begoña LópezJavier Díez
Feb 27, 2021·American Journal of Physiology. Heart and Circulatory Physiology·Brittany O AicherAreck A Ucuzian
Mar 11, 2020·Progress in Retinal and Eye Research·J Sebag
Aug 24, 2021·Journal of Vascular Surgery. Vascular Science·Shin-Rong LeeAlan Dardik
Sep 30, 2021·Biomedical Materials·Wenyu KongYanan Du

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