title: 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.
authors: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, People's Republic of China.
authors: Jing
authors: J
authors: Xie
authors: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, People's Republic of China; Department of Engineering Mechanics, Taiyuan University of Technology, Taiyuan 030024, People's Republic of China.
authors: Quanyou
authors: Q
authors: Zhang
authors: School of Life Science, Tsinghua University, Beijing 100084, People's Republic of China.
authors: Ting
authors: T
authors: Zhu
authors: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, People's Republic of China.
authors: Yanyan
authors: Y
authors: Zhang
authors: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, People's Republic of China.
authors: Bailin
authors: B
authors: Liu
authors: The First Affiliated Hospital of Guangxi University of Chinese Medicine, Nanning 530023, People's Republic of China.
authors: Jianwen
authors: J
authors: Xu
authors: Institute of Biomechanics and Medical Engineering, Department of Engineering Mechanics, Tsinghua University, Beijing 100084, People's Republic of China. Electronic address: zhaohc@mail.tsinghua.edu.cn.
authors: Hucheng
authors: H
authors: Zhao
mesh_terms: D000818:Animals; D001483:Base Sequence; D002642:Chick Embryo; D017931:DNA Primers; D005347:Fibroblasts / Q000201:enzymology; D005355:Fibrosis; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D016133:Polymerase Chain Reaction
chemical_list: D017931:DNA Primers; D020782:Matrix Metalloproteinases
keywords: Cardiac fibroblasts; Cardiac fibrosis; Gelatinases; Myocardial cells; Substrate stiffness