Mechanical and Chemical Regulation of Arterial and Venous Specification - Mechanical and Chemical Signaling in Angiogenesis - page 14

5.2 Habituation Model
This model explains arterial and venous specific phenotypes as seeds and states that
are required for them to correctly respond to mechanical forces generated by fluid
dynamics in arteries and veins, respectively (Fig. 4 b). According to this model,
chemical cues in the microenvironment in each endothelial cell induce genetic and
morphogenic changes that ''habituate'' them for the mechanical signals, to which they
are to be exposed. Therefore, one consequence of this model is that endothelial cells
fail to adapt and/or respond to specific mechanical forces generated by circulation
unless they are specified either to arterial or venous types by chemical and genetic
programs. Furthermore, endothelial cells of aberrant phenotypes with regard to arterial
or venous types may be malfunctional or dysfunctional under the normal circulation.
It has been long known that venous grafts in arterial vessels for cardiac bypass
surgery fail to adapt to arterial circulation. This may support the idea that arterial
and venous specific endothelial cell phenotypes established by genetic programs
are prerequisite for them to adapt and respond to their respective circulation.
5.3 Integrative Model
The third model is the one that integrates both morphogenetic and habituation
models. Certain genetic programs and chemical cues in the microenvironment
establish arterial and venous specific architecture of the vascular network. How-
ever, other genetic programs and chemical signals are to be used to build a chemical
signaling network in arterial and venous endothelial cells that allows them to adapt
and respond to specific mechanical forces generated by the respective circulation.
These three models are distinguishable and are experimentally testable. In the
past 15 or so years, we gained increasing knowledge on genetic and chemical
regulation of arterial and venous specification. With further identification of
arterial and venous specific genetic codes and formulation of testable models such
as those discussed in this section, it is anticipated that we are nearing towards the
complete understanding of the mechanisms underlying arteriovenous specification.
Acknowledgments The writing of this topic chapter was financially supported by JSPS (Kiban S),
Takeda Science Foundation and The Uehara Memorial Foundation to T.N.S.
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