VEGF gene therapy cooperatively recruits molecules from the immune system and stimulates cell homing and angiogenesis in refractory angina.
BACKGROUND
New vessels are formed in response to stimuli from angiogenic factors, a process in which paracrine signaling is fundamental.


OBJECTIVE
To investigate the cooperative paracrine signaling profile in response to Vascular Endothelial Growth Factor (VEGF) gene therapy in patients with coronary artery disease (CAD) and refractory angina.


METHOD
A cohort study was conducted in which plasma was collected from patients who underwent gene therapy with a plasmid expressing VEGF 165 (10) and from surgical procedure controls (4). Blood samples were collected from both groups prior to baseline and on days 3, 9 and 27 after the interventions and subjected to systemic analysis of protein expression (Interleukin-6, IL-6; Tumor Necrosis Factor-α, TNF-α; Interleukin-10, IL-10; Stromal Derived Factor-1 α, SDF-1α; VEGF; Angiopoietin-1, ANGPT-1; and Endothelin-1, ET-1) using the enzyme-linked immunosorbent assay (ELISA).


RESULTS
Analysis showed an increase in proinflammatory IL-6 (p=0.02) and ET-1 (p=0.05) on day 3 after gene therapy and in VEGF (p=0.02) on day 9. A strong positive correlation was found between mobilization of endothelial progenitor cells and TNF-α on day 9 (r=0.71; p=0.03). Furthermore, a strong correlation between β-blockers, antiplatelets, and vasodilators with SDF-1α baseline in the group undergoing gene therapy was verified (r=0.74; p=0.004).


CONCLUSION
Analysis of cooperative paracrine signaling after VEGF gene therapy suggests that the immune system cell and angiogenic molecule expression as well as the endothelial progenitor cell mobilization are time-dependent, influenced by chronic inflammatory process and continuous pharmacological treatment.
['Eibel|Bruna|B|', 'Markoski|Melissa M|MM|', 'Rodrigues|Clarissa G|CG|', 'Dipp|Thiago|T|', 'de Salles|Felipe B|FB|', 'Giusti|Imarilde I|II|', 'Nardi|Nance B|NB|', 'Plentz|Rodrigo D M|RD|', 'Kalil|Renato A K|RA|']
D000368:Aged D000787:Angina Pectoris D003324:Coronary Artery Disease D066026:Endothelial Progenitor Cells D005260:Female D015316:Genetic Therapy D006801:Humans D008297:Male D008875:Middle Aged D018919:Neovascularization, Physiologic D019899:Paracrine Communication D042461:Vascular Endothelial Growth Factor A
Gene therapy Cell homing Angiogenesis Refractory angina Vascular endothelial growth factor Coronary artery disease