Biomedical Engineering Reference
In-Depth Information
cytokines and chemokines (e.g., interleukin-1, IL-1, and monocyte chemoattrac-
tant protein, MCP-1), and clotting factors (e.g., tPA)—all in response to changing
mechanical stimuli including local stresses or trauma. See Refs. [
19
,
28
] for more
on endothelial mechanobiology.
The structure of smooth muscle differs from that of skeletal and cardiac muscle,
but its contractility also depends on a calcium dependent actin-myosin interaction.
Vascular smooth muscle can generate contractile forces comparable to those of
striated muscles while maintaining the contraction for longer periods and at a
lower expenditure of energy. This feature allows blood vessels to maintain a
''basal tone'' from which they can dilate or constrict further. Like ECs, SMCs
respond to changes in their mechanical environment; for example, SMCs alter
their synthesis of collagen in response to changes in mechanical loading.
Mechanical damage to elastin can also induce phenotypic changes in smooth
muscle that promote migration, proliferation, and apoptosis in addition to synthesis
of matrix. This causality appears to be fundamental to the response of the arterial
wall to clinical interventions such as balloon angioplasty and stenting and likewise
to the response of the venous wall to its clinical use as an arterial by-pass graft. See
Refs. [
42
,
68
] for more on the mechanobiology of smooth muscle.
Fibroblasts are primarily responsible for regulating the extracellular matrix in
the adventitia, as, for example, via synthesis and degradation of collagen. Deg-
radation is accomplished via ingestion by cells (phagocytosis) or the release of
enzymes, including the matrix metalloproteinases (MMPs). Fibroblasts play an
important role in regulating the ECM in many soft tissues (from the eye to the skin
to heart tissue) and are easily studied in vitro. For these reasons, there is a con-
siderable literature on the mechanobiology of fibroblasts and myofibroblasts (e.g.,
[
59
]). Macrophages are scavenger cells; in response to a local injury, they enter the
vessel wall from the blood (actually blood borne monocytes adhere to the wall and
transform into macrophages while inside the wall) and act primarily via phago-
cytosis or the release of MMPs. They, too, are responsive to changes in mechanical
stimuli [
64
]. Platelets also circulate within the bloodstream; they play a key role in
coagulation, but also release growth factors (e.g., PDGF) and vasoconstrictors
(e.g., serotonin, 5-HT, and thromboxane, TXA
2
) that affect both ECs and SMCs.
Platelet derived vasoconstrictors play a particularly damaging role following the
rupture of intracranial aneurysms, causing nearby vessels to constrict and cause
distal strokes. More specifics of the molecular biology of blood borne cells can be
found in general textbooks.
2.2 Key Signaling Pathways in Vascular Adaptation
Myriad signaling pathways play important roles in vascular homeostasis and
adaptation in both large and small vessels. Many of these molecules are homol-
ogous across species and play important roles in mediating homeostasis and
growth in other organ systems. For example, VEGF is a highly conserved family
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