Induction of LOX by TGF‐β1/Smad/AP‐1 signaling aggravates rat myocardial fibrosis and heart failure

This study aims to evaluate the efficacy of lysyl oxidase (LOX) inhibition in regulating rat myocardial fibrosis and chronic heart failure (CHF) and to validate the regulation of LOX by TGF‐β1/Smad2/3 signaling in this process. A rat model of CHF was established by abdominal aortic coarctation. The...

Full description

Saved in:
Bibliographic Details
Published in:IUBMB life 2019-11, Vol.71 (11), p.1729-1739
Main Authors: Lu, Min, Qin, Qingzhu, Yao, Jungong, Sun, Lin, Qin, Xinglei
Format: Article
Language:English
Subjects:
ACE2
Aldosterone
Angiotensin
Angiotensin II
Angiotensin-converting enzyme 2
Aorta
Cell proliferation
chronic heart failure
Collagen
Collagen (type I)
Congestive heart failure
c‐Jun
Fibroblasts
Fibrosis
Heart failure
Hydroxyproline
Kinases
LOXSmadTGF‐β1
Lysyl oxidase
Renin
Smad protein
Smad2 protein
Transforming growth factor-b1
Ventricle
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:This study aims to evaluate the efficacy of lysyl oxidase (LOX) inhibition in regulating rat myocardial fibrosis and chronic heart failure (CHF) and to validate the regulation of LOX by TGF‐β1/Smad2/3 signaling in this process. A rat model of CHF was established by abdominal aortic coarctation. The renin‐angiotensin‐aldosterone system (RAAS) indexes (PRA, ACE2, Ang II, and ALD), cardiac function indicators (LVEF, LVFS, SAP, DAP, and LVEDP), ventricular remodeling‐ and fibrosis‐related indicators (hydroxyproline, collagen deposition,and MMP‐2/9), and morphological changes of myocardial tissues were examined. Rat cardiac fibroblasts (RCFs) were used in vitro assays. CHF patients showed increased LOX activity, accompanied by activated RAAS and TGF‐β1. Furthermore, inhibition of LOX by β‐aminopropionitrile (BAPN) mitigated the RAAS activation and attenuated cardiac dysfunction, ventricular remodeling, myocardial fibrosis, and collagen deposition in CHF rats. Moreover, TGF‐β1 signaling diminished the LOX inhibition‐mediated antiheart failure effect. Further assays showed that TGF‐β1/Smad2/3 signaling increased expression of c‐jun (AP‐1 transcription factor subunit), which transcriptionally induced LOX expression. Additionally, BAPN abrogated the TGF‐β1‐mediated increase in cell proliferation and levels of MMP‐2/9 and collagen I/III in RCFs. In conclusion, LOX can be induced by TGF‐β1/Smad/AP‐1 signaling and LOX inhibition attenuates rat myocardial fibrosis and CHF.
ISSN:1521-6543
1521-6551
DOI:10.1002/iub.2112