Vascular Endothelium - Tissue Functioning and Remodeling in the Circulatory and Ventilatory Systems - page 567

Steady pressurization 156 of isolated rat cerebral and mesenteric arteries decreases
Fos expression in the cerebral arteries subjected to 18.6 kPa compared with 10.6 kPa
(control), but not in mesenteric arteries [ 1054 ].
Vascular endothelial cell are subjected to intercellular junctional and intracellular
tensions. Under static conditions, cells in confluent monolayers are subjected to
uniform intracellular tensions from cell junctions to cell edges [ 1055 ]. When a
mechanical stress is applied with a mean forward component, focal adhesion sites
change and stress fibers and intracellular tensions orientate mainly in the streamwise
direction. Intracellular tension may follow the path of the stress fibers with adherens
junctions at upstream and downstream ends [ 1055 ]. When the mechanical stress
oscillates with a very low mean, intracellular tensions do not have a preferential
orientation [ 1055 ].
Stretch-mediated signaling by elastin-laminin receptors reduces Fos expression
and subsequent cellular proliferation. Mechanosensitive signaling via elastin-
laminin receptors hence depends on the artery type and/or perfusion territory (e.g.,
cerebral vs. mesenteric circulation).
Mechanical stresses either promote or repress gene expression in endothelial
cells. A small fraction of targeted genes respond to mechanical stresses [ 1056 ].
In general, mechanical stimuli promote expression of transcription activators or
repressors Fos and Jun. Mechanical stresses also activate another transcription
promoter, the mechanical stress response element [ 1057 ]. The latter is found in
promoters of genes that encode platelet-derived growth factor-A and -B, tissue
plasminogen activator, transforming growth factor-

β 1, and intercellular adhesion

molecule ICAM1.

9.10.1 Transducers of Mechanical Stresses

Several types of mediators are targeted by mechanotransduction (Fig. 9.8 ). They
locatize: (1) either on the endothelium wetted surface; (2) on the lateral walls (cell-
cell junctions); (3) on the abluminal membrane (cell-matrix junctions), or (4) within
the cytoplasm. Three-dimensional conformational changes of membrane proteins
induced by applied stresses can initiate the cell response. Mechanical transduction
uses a set of messengers and leads to gene transcription.
Various mechanosensors detect stresses and strains applied to the endothelial
cells (Fig. 9.8 ). Transduction surface elements include: (1) mechanosensitive ion
carriers, especially stress-gated ion channels; (2) plasmalemmal receptors, such as
receptor Tyr kinases and G-protein-coupled receptors; (3) adhesion molecules of in-
tercellular and matrix-cell junctions that are associated with cytoskeletal filaments;

156 Isolated arteries are subjected to 8.6 kPa during 2 h, then to a step pressure increase of either
10.6 or 18.6 kPa during 30 mn.