Journal article icon

Journal article

Mechanisms responsible for increased circulating levels of galectin-3 in cardiomyopathy and heart failure

Abstract:
Galectin-3 is a biomarker of heart disease. However, it remains unknown whether increase in galectin-3 levels is dependent on aetiology or disease-associated conditions and whether diseased heart releases galectin-3 into the circulation. We explored these questions in mouse models of heart disease and in patients with cardiomyopathy. All mouse models (dilated cardiomyopathy, DCM; fibrotic cardiomyopathy, ischemia-reperfusion, I/R; treatment with β-adrenergic agonist isoproterenol) showed multi-fold increases in cardiac galectin-3 expression and preserved renal function. In mice with fibrotic cardiomyopathy, I/R or isoproterenol treatment, plasma galectin-3 levels and density of cardiac inflammatory cells were elevated. These models also exhibited parallel changes in cardiac and plasma galectin-3 levels and presence of trans-cardiac galectin-3 gradient, indicating cardiac release of galectin-3. DCM mice showed no change in circulating galectin-3 levels nor trans-cardiac galectin-3 gradient or myocardial inflammatory infiltration despite a 50-fold increase in cardiac galectin-3 content. In patients with hypertrophic cardiomyopathy or DCM, plasma galectin-3 increased only in those with renal dysfunction and a trans-cardiac galectin-3 gradient was not present. Collectively, this study documents the aetiology-dependency and diverse mechanisms of increment in circulating galectin-3 levels. Our findings highlight cardiac inflammation and enhanced β-adrenoceptor activation in mediating elevated galectin-3 levels via cardiac release in the mechanism.
Publication status:
Published
Peer review status:
Peer reviewed

Actions

Access Document

Publisher copy:
10.1038/s41598-018-26115-y

Authors

More by this author
Institution:
University of Oxford
Division:
MSD
Department:
RDM
Sub department:
RDM Cardiovascular Medicine
Role:
Author


Publisher:
Nature Publishing Group
Journal:
Scientific Reports More from this journal
Volume:
8
Pages:
8213
Publication date:
2018-05-29
Acceptance date:
2018-04-16
DOI:
EISSN:
2045-2322
ISSN:
2045-2322


Keywords:
Pubs id:
pubs:856598
UUID:
uuid:c7c7e76a-46c1-4bf6-9c4e-5a42d019a26f
Local pid:
pubs:856598
Source identifiers:
856598
Deposit date:
2018-06-08
ARK identifier:

Terms of use


Views and Downloads






If you are the owner of this record, you can report an update to it here: Report update to this record

TO TOP