Mechanosensory Pathways in Angiocrine Mediated Tissue Regeneration - Mechanical and Chemical Signaling in Angiogenesis - page 22

layer is rich in vascular smooth muscle, which serves to control the caliber of the
vessel. Taken together, these cells experience cyclic stretch when they serve to
modulate vasodilation and vasoconstriction as well as control blood rheology [ 19 ].
By virtue of its location, the endothelium has an important role as the primary
interface between circulating blood and the vascular wall. Endothelial cells in
particular sense blood flow and shear stress. The role of biomechanical forces in
the ability to regenerate tissues and thus restore the function of damaged or dis-
eased organs requires clarification.
3 Biomechanical Forces
Traditionally, it has been thought that biochemical signals serve as the main method
in which signaling pathways are activated in endothelial cells. However, new
research has determined that mechanical forces experienced by endothelial cells
have a significant impact on cell phenotype and function. Biomechanical forces play
essential roles in tissue and organ development [ 20 ]. Recent studies have demon-
strated that mechanical forces can regulate endothelial cell proliferation, survival,
migration [ 21 ], and ECM remodeling, and hence influence angiogenesis [ 22 ].
Mechanosensitivity describes the ability of cells to perceive mechanical stimuli and
interpret them into biological signals at the molecular level [ 23 ]. As such, mecha-
notransduction is a set of fundamental physiological mechanisms that allow cells to
react to physical forces. Mechanical stretch resulting from pulsatile blood flow can
modulate differentiation, proliferation and production of paracrine (angiocrine)
factors of vascular cell. In this mechanotransduction-based response of the arterial
system, numerous endothelial cellular components such as proteoglycans have a
crucial role [ 24 , 25 ].
3.1 Effect of Mechanical Stress on Endothelial Cells
Cells in the vascular system are subjected to mechanical forces due to the pulsatile
nature of blood flow. Endothelial cells and smooth muscle cells in the vessel wall
experience these mechanical forces the most. Mechanical stretch, resulting from
changes in blood pressure, can modulate several different cellular functions in
vascular smooth muscle cells. Our data provides a new framework in which to
consider how physical forces and molecular signals synchronize during the pro-
gram of liver regeneration (Fig. 1 ).
The effect of shear stress on vascular endothelial cells has been extensively
analyzed. There is a large body of evidence showing that it directly influences the
expression of many adhesive molecules like VCAM-1 [ 30 ] and ICAM-1 [ 31 ] and
mediator systems such as TGF-b [ 32 ] and nitric oxide synthase [ 33 ]. Several
groups of molecules have been shown to play a role in the detection of flow shear