106
3 Arteriogenesis
Arteriogenesis (enlargement of diameter of existing vessels) is typically conducted
first after exercise. Important function plays increased blood pressure together with
shear stress, which act as a mechanical stimulus for endothelial cells [ 21 , 22 ]. These
start to produce cocktail of cytokines as monocyte chemoattractant protein-1 (MCP-
1), FGF2, vascular endothelial growth factor (VEGF) or TNF-α that all have posi-
tive effect on arteriogenesis [ 23 , 24 ]. After arteriogenesis comes process of
angiogenesis, mainly when arteriogenesis itself is not able to cover demands of tis-
sues. It is an angiogenesis, which is superior to arteriogenesis when talking about
effective improvement of exchange properties between blood and tissue.
4 Angiogenesis
There are only few physiological circumstances prompting angiogenesis, notably
ovarian cycling or placental development. And exercise is one of them [ 25 ].
Essentially, there are two basic pathways for creation of a new mass of functional
vessels – sprouting angiogenesis and intussusceptive (non-sprouting) angiogenesis
(intussusception). And in the same time, this is the only effective process which is
apt to continuously establish improving exchange properties between blood and tis-
sue (Table 7.1).
Sprouting angiogenesis consists of the expansion and remodeling of existingvessels, where the vascular sprouts connect each other to form new vascular loops
[ 26 ]. Intussusception allows a vast increase in the number of capillaries without a
corresponding increase in the number of endothelial cells (no need for activation of
endogenous endothelial stem cells). Blood vessels are generated more rapidly in an
energetically and metabolically more economic manner, as extensive cell prolifera-
tion, basement membrane degradation, and invasion of the surrounding tissue are
not required. Mechanical triggers for intussusception are similar as those for arterio-
genesis [ 27 ].
For those interested, the detailed process of intussusceptive angiogenesis, it isalready excellently and comprehensively described elsewhere (e.g. [ 29 ]). There is a
study from Prior et al. [ 25 ] telling that exercise with subsequent muscle contractions
Table 7.1 Sequence of
events in sprouting
angiogenesis
- Angiogenic growth factors
- Activation of receptors on
endothelial cells - Release of proteases
(metalloproteinases like MMP-2)
that destroy BM - Formation of solid sprouts
from migrating endothelial cells - Luminization of sprouts
M. Miko and I. Varga