TY - JOUR
T1 - Novel mechanisms of endothelial mechanotransduction
AU - Abe, Jun Ichi
AU - Berk, Bradford C.
N1 - Publisher Copyright:
© 2014 American Heart Association, Inc.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - Atherosclerosis is a focal disease that develops preferentially where nonlaminar, disturbed blood flow occurs, such as branches, bifurcations, and curvatures of large arteries. Endothelial cells sense and respond differently to disturbed flow compared with steady laminar flow. Disturbed flow that occurs in so-called atheroprone areas activates proinflammatory and apoptotic signaling, and this results in endothelial dysfunction and leads to subsequent development of atherosclerosis. In contrast, steady laminar flow as atheroprotective flow promotes expression of many anti-inflammatory genes, such as Kruppel-like factor 2 and endothelial nitric oxide synthase and inhibits endothelial inflammation and athrogenesis. Here we will discuss that disturbed flow and steady laminar flow induce pro- and antiatherogenic events via flow type-specific mechanotransduction pathways. We will focus on 5 mechanosensitive pathways: mitogen-activated protein kinases/ extracellular signal-regulated kinase 5/Kruppel-like factor 2 signaling, extracellular signal-regulated kinase/peroxisome proliferator-activated receptor signaling, and mechanosignaling pathways involving SUMOylation, protein kinase C-æ, and p90 ribosomal S6 kinase. We think that clarifying regulation mechanisms between these 2 flow types will provide new insights into therapeutic approaches for the prevention and treatment of atherosclerosis.
AB - Atherosclerosis is a focal disease that develops preferentially where nonlaminar, disturbed blood flow occurs, such as branches, bifurcations, and curvatures of large arteries. Endothelial cells sense and respond differently to disturbed flow compared with steady laminar flow. Disturbed flow that occurs in so-called atheroprone areas activates proinflammatory and apoptotic signaling, and this results in endothelial dysfunction and leads to subsequent development of atherosclerosis. In contrast, steady laminar flow as atheroprotective flow promotes expression of many anti-inflammatory genes, such as Kruppel-like factor 2 and endothelial nitric oxide synthase and inhibits endothelial inflammation and athrogenesis. Here we will discuss that disturbed flow and steady laminar flow induce pro- and antiatherogenic events via flow type-specific mechanotransduction pathways. We will focus on 5 mechanosensitive pathways: mitogen-activated protein kinases/ extracellular signal-regulated kinase 5/Kruppel-like factor 2 signaling, extracellular signal-regulated kinase/peroxisome proliferator-activated receptor signaling, and mechanosignaling pathways involving SUMOylation, protein kinase C-æ, and p90 ribosomal S6 kinase. We think that clarifying regulation mechanisms between these 2 flow types will provide new insights into therapeutic approaches for the prevention and treatment of atherosclerosis.
KW - ERK5
KW - PKζ
KW - SUMOylation
KW - flow
UR - http://www.scopus.com/inward/record.url?scp=84911941197&partnerID=8YFLogxK
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U2 - 10.1161/ATVBAHA.114.303428
DO - 10.1161/ATVBAHA.114.303428
M3 - Review article
C2 - 25301843
AN - SCOPUS:84911941197
SN - 1079-5642
VL - 34
SP - 2378
EP - 2386
JO - Arteriosclerosis, thrombosis, and vascular biology
JF - Arteriosclerosis, thrombosis, and vascular biology
IS - 11
ER -