Growth Factor Delivery Systems for the Treatment of Cardiovascular Diseases - Biointerfaces: Where Material Meets Biology - page 88

PDGF was used in an attempt to improve skeletal myoblast ecacy in a rat
model of MI. While no statistical progress was seen in left ventricular
function within the treatment groups, the sustained delivery PDGF did im-
prove angiogenesis, cardiomyocyte survival, and long-term function. 15

d n 3 r 4 n g | 4

4.3.1.4 Angiopoietins
The best known proteins of this family are Ang-1 and Ang-2 and they seem to
act as antagonists of each other in several cardiovascular remodeling and
vascular processes. Ang-1, which is expressed by pericytes, may limit
angiogenesis and its deletion leads to excessive angiogenesis and tissue fi-
brosis. In contrast, Ang-2 is expressed by endothelial cells and may regulate
cell-matrix interactions in growing vessels. 18
Human Ang-1 and VEGF were co-encapsulated in albumin nanoparticles
for controlled delivery. The results indicated that the released proteins were
biologically active and the combined application of both proteins demon-
strated a significant highly proliferative and antiapoptotic effect on human
umbilical vein endothelial cells (HUVECs) as compared with the effect
demonstrated by each proteins alone. 94
A further study demonstrated that a thermoresponsive hydrogel made of
chitosan, conjugated with Ang-1 and mixed with collagen, allowed in vitro
survival and maintenance of function of neonatal rat cardiomyocytes in
comparison to unmodified chitosan-collagen hydrogels. Additionally, this
group demonstrated that the hydrogel is suitable for subcutaneous cell in-
jection and that it can be localized in the infarcted zone of mouse heart. 95
Recently, Anisimov et al. manufactured a VEGF-angiopoietin-1 chimera and
confirmed its angiogenic potential by triggering, in a novel fashion, VEGF
receptor-2. This chimera promoted less vessel leakiness, less tissue inflam-
mation and better perfusion in ischemic muscle than VEGF alone. 96 Further
development in angiogenesis will offer a better understanding of the role
that angiopoietins play in response to ischemic insult and as potential
therapeutic agents.

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4.3.2 Direct Effect on Cardiac Cell Proliferation, Remodeling,
Tissue Protection and Differentiation
The maintenance of cardiomyocyte number and growth of surviving cardi-
omyocytes are two important factors that modulate preservation of myo-
cardial function in response to stress.

4.3.2.1 Fibroblast Growth Factor
Several members of this family have been used in DDS for cardiovascular
diseases either to promote angiogenesis, 17,97,98 differentiation or a com-
bination of both effects. 99 Under experimental conditions it has been proved