title: Mechanoregulation of cardiac myofibroblast differentiation: implications for cardiac fibrosis and therapy.
abstract: Cardiac myofibroblast differentiation, as one of the most important cellular responses to heart injury, plays a critical role in cardiac remodeling and failure. While biochemical cues for this have been extensively investigated, the role of mechanical cues, e.g., extracellular matrix stiffness and mechanical strain, has also been found to mediate cardiac myofibroblast differentiation. Cardiac fibroblasts in vivo are typically subjected to a specific spatiotemporally changed mechanical microenvironment. When exposed to abnormal mechanical conditions (e.g., increased extracellular matrix stiffness or strain), cardiac fibroblasts can undergo myofibroblast differentiation. To date, the impact of mechanical cues on cardiac myofibroblast differentiation has been studied both in vitro and in vivo. Most of the related in vitro research into this has been mainly undertaken in two-dimensional cell culture systems, although a few three-dimensional studies that exist revealed an important role of dimensionality. However, despite remarkable advances, the comprehensive mechanisms for mechanoregulation of cardiac myofibroblast differentiation remain elusive. In this review, we introduce important parameters for evaluating cardiac myofibroblast differentiation and then discuss the development of both in vitro (two and three dimensional) and in vivo studies on mechanoregulation of cardiac myofibroblast differentiation. An understanding of the development of cardiac myofibroblast differentiation in response to changing mechanical microenvironment will underlie potential targets for future therapy of cardiac fibrosis and failure.
authors.affiliation: Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an, People's Republic of China; Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, Malaysia; and.
authors.forename: Kar Wey
authors.initials: KW
authors.lastname: Yong
authors.affiliation: Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an, People's Republic of China; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: YuHui
authors.initials: Y
authors.lastname: Li
authors.affiliation: Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an, People's Republic of China; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: GuoYou
authors.initials: G
authors.lastname: Huang
authors.affiliation: Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an, People's Republic of China;
authors.forename: Tian Jian
authors.initials: TJ
authors.lastname: Lu
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, Malaysia; and.
authors.forename: Wan Kamarul Zaman Wan
authors.initials: WK
authors.lastname: Safwani
authors.affiliation: Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, Kuala Lumpur, Malaysia; and.
authors.forename: Belinda
authors.initials: B
authors.lastname: Pingguan-Murphy
authors.affiliation: Bioinspired Engineering and Biomechanics Center, Xi'an Jiaotong University, Xi'an, People's Republic of China; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China fengxu@mail.xjtu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Xu
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005109:Extracellular Matrix / Q000378:metabolism; D005355:Fibrosis / Q000378:metabolism / Q000628:therapy; D006801:Humans; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology; D058628:Myofibroblasts / Q000166:cytology* / Q000378:metabolism / Q000502:physiology; D013314:Stress, Mechanical; D023822:Tissue Engineering
keywords: ECM stiffness; cardiac myofibroblast differentiation; mechanical cues; mechanical microenvironment; mechanical strain