TY - JOUR
T1 - The interplay of signaling pathway in endothelial cells—matrix stiffness dependency with targeted-therapeutic drugs
AU - Vania, Vicki
AU - Wang, Lu
AU - Tjakra, Marco
AU - Zhang, Tao
AU - Qiu, Juhui
AU - Tan, Youhua
AU - Wang, Guixue
PY - 2020/5/1
Y1 - 2020/5/1
N2 - Cardiovascular diseases (CVDs) have been one of the major causes of human deaths in the world. The study of CVDs has focused on cell chemotaxis for decades. With the advances in mechanobiology, accumulating evidence has demonstrated the influence of mechanical stimuli on arterial pathophysiology and endothelial dysfunction that is a hallmark of atherosclerosis development. An increasing number of drugs have been exploited to decrease the stiffness of vascular tissue for CVDs therapy. However, the underlying mechanisms have yet to be explored. This review aims to summarize how matrix stiffness mediates atherogenesis through various important signaling pathways in endothelial cells and cellular mechanophenotype, including RhoA/Rho-associated protein kinase (ROCK), mitogen-activated protein kinase (MAPK), and Hippo pathways. We also highlight the roles of putative mechanosensitive non-coding RNAs in matrix stiffness-mediated atherogenesis. Finally, we describe the usage of tunable hydrogel and its future strategy to improve our knowledge underlying matrix stiffness-mediated CVDs mechanism.
AB - Cardiovascular diseases (CVDs) have been one of the major causes of human deaths in the world. The study of CVDs has focused on cell chemotaxis for decades. With the advances in mechanobiology, accumulating evidence has demonstrated the influence of mechanical stimuli on arterial pathophysiology and endothelial dysfunction that is a hallmark of atherosclerosis development. An increasing number of drugs have been exploited to decrease the stiffness of vascular tissue for CVDs therapy. However, the underlying mechanisms have yet to be explored. This review aims to summarize how matrix stiffness mediates atherogenesis through various important signaling pathways in endothelial cells and cellular mechanophenotype, including RhoA/Rho-associated protein kinase (ROCK), mitogen-activated protein kinase (MAPK), and Hippo pathways. We also highlight the roles of putative mechanosensitive non-coding RNAs in matrix stiffness-mediated atherogenesis. Finally, we describe the usage of tunable hydrogel and its future strategy to improve our knowledge underlying matrix stiffness-mediated CVDs mechanism.
KW - Cardiovascular disease
KW - Endothelial cell
KW - Hippo pathway
KW - MAPK
KW - Matrix stiffness
KW - RhoA/ROCK
UR - http://www.scopus.com/inward/record.url?scp=85077319467&partnerID=8YFLogxK
U2 - 10.1016/j.bbadis.2019.165645
DO - 10.1016/j.bbadis.2019.165645
M3 - Review article
C2 - 31866415
AN - SCOPUS:85077319467
VL - 1866
JO - Biochimica et Biophysica Acta - Molecular Basis of Disease
JF - Biochimica et Biophysica Acta - Molecular Basis of Disease
SN - 0925-4439
IS - 5
M1 - 165645
ER -