Intramyocardial transplantation of fibroblasts expressing vascular endothelial growth factor attenuates cardiac dysfunction.
In this study, we analyzed whether transplantation of cardiac fibroblasts (CFs) expressing vascular endothelial growth factor (VEGF) mitigates cardiac dysfunction after myocardial infarction (MI) in rats. First, we observed that the transgene expression lasts longer (45 vs 7 days) when fibroblasts are used as vectors compared with myoblasts. In a preventive protocol, induction of cardiac neovascularization accompanied by reduction in myocardial scar area was observed when cell transplantation was performed 1 week before ischemia/reperfusion and the animals analyzed 3 weeks later. Finally, the therapeutic efficacy of this approach was tested injecting cells in a fibrin biopolymer, to increase cardiac retention, 24 h post-MI. After 4 weeks, an increase in neovascularization and a decrease in myocardial collagen were observed only in rats that received cells expressing VEGF. Basal indirect or direct hemodynamic measurements showed no differences among the groups whereas under pharmacological stress, only the group that received cells expressing VEGF showed a significant reduction in end-diastolic pressure and improvement in stroke volume and cardiac work. These results indicate that transplantation of CFs expressing VEGF using fibrin biopolymer induces neovascularization and attenuates left ventricle fibrosis and cardiac dysfunction in ischemic heart.
Gonçalves
G A
GA
Department of Medicine, Heart Institute InCor, University of Sao Paulo Med Sch, Sao Paulo, Brazil.
Vassallo
P F
PF
dos Santos
L
L
Schettert
I T
IT
Nakamuta
J S
JS
Becker
C
C
Tucci
P J F
PJ
Krieger
J E
JE
D000818:Animals; D005337:Fibrin / Q000008:administration & dosage; D005347:Fibroblasts / Q000378:metabolism / Q000637:transplantation*; D015316:Genetic Therapy / Q000379:methods*; D008297:Male; D009203:Myocardial Infarction / Q000517:prevention & control / Q000628:therapy*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control / Q000628:therapy; D018919:Neovascularization, Physiologic / Q000235:genetics; D051381:Rats; D011917:Rats, Inbred Lew; D019076:Transgenes; D042442:Vascular Endothelial Growth Factors / Q000235:genetics*
D042442:Vascular Endothelial Growth Factors; D005337:Fibrin