Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 583

involved in the vascular tone in response to local flow pattern. Isotype KLF2 acts on
the synthesis of nitric oxide as well as endothelin-1 and adrenomedullin. In steady
and pulsatile flows, high hemodynamic stresses increase KLF2 expression, whereas
cyclic stretch has no effect [ 1126 ].

9.10.6.2 P53 and MicroRNAs

In endothelial cells exposed to a prolonged (24 h), steady, laminar flow triggers an
antiproliferative and anti-inflammatory response. Laminar flow-induced endothelial
cell growth arrest involves CDK inhibitors and P53 transcription factor. In addition,
mechanical stress mediates P53-dependent apoptosis of smooth myocytes via the
P38MAPK pathway [ 1127 ].
In human umbilical vein endothelial cells subjected to steady laminar flow,
miR19a attenuates the expression of a reporter gene controlled by a conserved 3 -
untranslated region of the cyclin-D1 gene, hence synthesis of cyclin-D1 that causes
a cell cycle arrest at the G1-S transition [ 1128 ].
Endothelial cell growth arrest also results from pulsatile flow. In response to
24-h pulsatile flow, 8 (e.g., miR23b and miR27b) and 13 microRNAs (e.g., miR16,
miR17, and miR221) are up- and downregulated in cultured endothelial cells,
respectively, w.r.t. static condition [ 1129 ]. MicroRNA-23b causes E2F1 reduction
and hypophosphorylation of retinoblastoma protein, thereby eliciting G0-G1 arrest.

9.10.6.3 Small Monomeric GTPases

Small GTPase CDC42 173 is activated by hemodynamic stress via interactions be-
tween stimulated integrins 174 and the extracellular matrix via Par6 and PKC [ 1130 ]

(Fig. 9.8 ). Furthermore, in flow-stimulated endothelial cells, Rac1 GTPase is also
activated from integrin-matrix binding.

ζ

9.10.6.4 Thioredoxin

Endothelial cells subjected to blood stresses not only secrete regulators of the
vasomotor tone, but also act on other local biological phenomena, such as inflam-
mation (Sect. 11.5 ). Thioredoxin-interacting protein (TxnIP) 175 and thioredoxin

173 Small GTPase CDC42 is implicated in cell polarity, inducing reorientation of the microtubule
organizing center and Golgi body toward the motion direction.
174 Hemodynamic stress activates particularly

β 3 -integrins and increases integrin binding to the
extracellular matrix that inhibits Rho GTPase. This transient inhibition is required for cytoskeletal
alignment in the flow direction.
175 Thioredoxin-interacting protein is also known as vitamin-D-upregulating protein-1.

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