The Mechanobiology of Endothelial-to-Mesenchymal Transition in Cardiovascular Disease

Frontiers in Physiology

卷:12

Yin Tintut¹  Dino Di Carlo³  Shahrin Islam⁶  Yucheng Yao⁶  Craig A. Simmons⁸  Kristina I. Boström¹⁰  Jeffrey J. Hsu¹⁰ 

[1] 0Department of Orthopedic Surgery, University of California, Los Angeles, Los Angeles, CA, United States;

[2] Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, United States;

[3] Department of Electrical and Computer Engineering, University of California, Los Angeles, Los Angeles, CA, United States;

[4] Department of Mechanical and Industrial Engineering, University of Toronto, Toronto, ON, Canada;

[5] Department of Physiology, University of California, Los Angeles, Los Angeles, CA, United States;

[6] Division of Cardiology, Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA, United States;

[7] Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada;

[8] Translational Biology and Engineering Program, Ted Rogers Centre for Heart Research, Toronto, ON, Canada;

[9] UCLA Molecular Biology Institute, Los Angeles, CA, United States;

[10] Veterans Affairs Greater Los Angeles Healthcare System, Los Angeles, CA, United States;

关键词: endothelial-to-mesenchymal transition;    mechanobiology;    cardiovascular disease;    endothelial;    mesenchymal;    biomechanical;   

DOI  :  10.3389/fphys.2021.734215

来源: DOAJ

【 摘 要 】

Endothelial cells (ECs) lining the cardiovascular system are subjected to a highly dynamic microenvironment resulting from pulsatile pressure and circulating blood flow. Endothelial cells are remarkably sensitive to these forces, which are transduced to activate signaling pathways to maintain endothelial homeostasis and respond to changes in the environment. Aberrations in these biomechanical stresses, however, can trigger changes in endothelial cell phenotype and function. One process involved in this cellular plasticity is endothelial-to-mesenchymal transition (EndMT). As a result of EndMT, ECs lose cell-cell adhesion, alter their cytoskeletal organization, and gain increased migratory and invasive capabilities. EndMT has long been known to occur during cardiovascular development, but there is now a growing body of evidence also implicating it in many cardiovascular diseases (CVD), often associated with alterations in the cellular mechanical environment. In this review, we highlight the emerging role of shear stress, cyclic strain, matrix stiffness, and composition associated with EndMT in CVD. We first provide an overview of EndMT and context for how ECs sense, transduce, and respond to certain mechanical stimuli. We then describe the biomechanical features of EndMT and the role of mechanically driven EndMT in CVD. Finally, we indicate areas of open investigation to further elucidate the complexity of EndMT in the cardiovascular system. Understanding the mechanistic underpinnings of the mechanobiology of EndMT in CVD can provide insight into new opportunities for identification of novel diagnostic markers and therapeutic interventions.

【 授权许可】

Unknown