Vascular Cell Physiology Under Shear Flow: Role of Cell Mechanics and Mechanotransduction - Mechanical and Chemical Signaling in Angiogenesis - page 136

Fig. 8 Polarization of MTOC in MPECs and non-patterned (NP) ECs [ 66 ]

for some molecules, such as thrombomodulin. This suggests that certain signaling
cascades are only activated after surpassing a specific mechanical threshold. Fur-
thermore, the additive effects on cytoskeletal alignment and fluid shear stress on
expression of VCAM-1, vWF, and TFPI implies that aligned cytoskeletal confor-
mation is required for optimal mechanical force-induced cytoskeletal signaling.
These complex signaling cascades would then affect other larger cellular structures,
such as the nucleus, where recent evidence [ 68 ] has demonstrated that failure in such
crosstalk at the sub-cellular and cellular levels may help explain why only certain
tissues and organs, including the cardiovascular system, mimic natural aging deg-
radation in progeria patients but not others [ 69 ]. Indeed, with the advancement in
high-content and high-throughput screening platforms, and increased awareness of
biophysical contributions, additional studies are needed to begin deciphering this
multi-scale dialogue in order to better understand the mechanisms of disease.

Acknowledgments This work was supported by the American Heart Association
09BGIA2260384 (M.T.H), and the National Institute of Health grants 1R01HL103728 (M.T.H.),
R01HL101972 (O.J.T.M.) and 1U54CA143906 (O.J.T.M.).

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