Substrate stiffness-regulated matrix metalloproteinase output in myocardial cells and cardiac fibroblasts: implications for myocardial fibrosis.

Abstract:

:Cardiac fibrosis, an important pathological feature of structural remodeling, contributes to ventricular stiffness, diastolic dysfunction, arrhythmia and may even lead to sudden death. Matrix stiffness, one of the many mechanical factors acting on cells, is increasingly appreciated as an important mediator of myocardial cell behavior. Polydimethylsiloxane (PDMS) substrates were fabricated with different stiffnesses to mimic physiological and pathological heart tissues, and the way in which the elastic modulus of the substrate regulated matrix-degrading gelatinases in myocardial cells and cardiac fibroblasts was explored. Initially, an increase in cell spreading area was observed, concomitant with the increase in PDMS stiffness in both cells. Later, it was demonstrated that the MMP-2 gene expression and protein activity in myocardial cells and cardiac fibroblasts can be enhanced with an increase in PDMS substrate stiffness and, moreover, such gene- and protein-related increases had a significant linear correlation with the elastic modulus. In comparison, the MMP-9 gene and protein expressions were up-regulated in cardiac fibroblasts only, not in myocardial cells. These results implied that myocardial cells and cardiac fibroblasts in the myocardium could sense the stiffness in pathological fibrosis and showed a differential but positive response in the expression of matrix-degrading gelatinases when exposed to an increased stiffening of the matrix in the microenvironment. The phenomenon of cells sensing pathological matrix stiffness can help to increase understanding of the mechanism underlying myocardial fibrosis and may ultimately lead to planning cure strategies.

journal_name

Acta Biomater

journal_title

Acta biomaterialia

authors

Xie J,Zhang Q,Zhu T,Zhang Y,Liu B,Xu J,Zhao H

doi

10.1016/j.actbio.2014.01.031

subject

Has Abstract

pub_date

2014-06-01 00:00:00

pages

2463-72

issue

6

eissn

1742-7061

issn

1878-7568

pii

S1742-7061(14)00049-X

journal_volume

10

pub_type

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