107
create a powerful stimulus for structural remodeling of the vasculature within the
random muscle. An increase in flow velocity through a vessel increases shear stress,
a major stimulus for enlargement of conduit vessels. This leads to an endothelial-
dependent, nitric oxide-dependent enlargement of the vessel. Increased flow within
muscle, in the absence of contractions, leads to an enhanced capillarity by intus-
susceptive angiogenesis [ 25 ] and even sprouting angiogenesis [ 5 ] (Table 7.2).
5 Neoangiogenesis Promoting Factors Playing Role
During Exercise
As a summary of the written, we try to give a closer look to main factors which stay
behind neoangiogenesis in the heart wall during exercise. We present them in a logi-
cal sequence of steps.
5.1 Mechanical – Hemodynamic Forces
Shear stress acting on endothelial surface induced by elevated radial stress and
increased blood flow are main factors which promote vessel caliber changes that
tend to restore baseline wall shear stress and that have been reported to be
endothelium- dependent [ 30 ] and, in the next step, they initiate consequent rise of
other angiogenic factors as cytokines. Muscle stretching itself is huge pro-
angiogenetic factor in skeletal muscle, however, for cardiac muscle; the role of its
increased performance during exercise is a question of further studies.
5.2 Angiogenic Biological Factors
Current thinking is that angiogenesis is mediated by diffusible angiogenic factors
and that angiogenic activity is regulated through the balance between stimulatory
and inhibitory factors [ 31 ]. Recent studies have shown that up-regulation of angio-
genic factors occurs in response to increased muscle activity in skeletal muscle [ 32 ].
Here we want to discuss some of the chosen biological active molecules incorpo-rated in pathways responsible for neoangiogenesis. We are also mentioning some
agents with opposite effect on neoangiogenesis (PEDF) or agents with positive
Table 7.2 Sequence of
events in intussusceptive
angiogenesis [ 28 ]
- Extension of capillary wall into
the lumen - Splitting of the vessel into two
new
7 Physical Exercise Can Spur Beneficial Neoangiogenesis andflMicrovasculature...