Vascular endothelial growth factor response in porcine coronary and peripheral arteries using nonsurgical occlusion model, local delivery, and liposome-mediated gene transfer.
Angiogenesis and arteriogenesis play an important role in advanced vascular occlusive diseases. Whether angiogenesis or arteriogenesis predominate depends on the preexisting collateral vessel network, the type and location of occlusion, and different developmental origin of the arteries. Angiogenesis and arteriogenesis were investigated following vascular endothelial growth factor (VEGF) treatment in different arteries important in occlusive arterial diseases using a newly developed porcine arterial occlusion model. Porcine coronary and peripheral arteries were occluded interventionally using blinded stent grafts. Gene transfer was performed using a needle injection catheter and cationic lipid DOCSPER as gene carrier. DNA and gene expression in arterial tissue was examined using polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR. Vessel development was determined by angiography, immunohistochemistry, and measurement of capillary density. The transfected gene and its expression were found 3 months following application. In tissue adjacent to coronary arteries, there was significantly enhanced capillary density but no increase in angiographic score. In contrast, tissue surrounding peripheral arteries demonstrated no enhancement of capillary density but an enhancement in angiographic score. These results demonstrate differential responses to VEGF treatment in coronary and peripheral arteries resulting predominantly in either angiogenesis or arteriogenesis. Further investigation of VEGF signaling pathway is necessary for better understanding of the processes of vascular development, which may have potential impact on the design of cardiovascular therapeutics.
Pelisek
Jaroslav
J
Department of Cardiology and Angiology, Universisty Hospital, Westfaelische Wilhelm University, Muenter, Germany.
Fuchs
Alexandra
A
Engelmann
Markus G
MG
Shimizu
Masumi
M
Golda
Adam
A
Mekkaoui
Choukri
C
Rolland
Pierre H
PH
Nikol
Sigrid
S
D042501:Angiogenic Proteins / Q000378:metabolism; D000818:Animals; D001157:Arterial Occlusive Diseases / Q000473:pathology / Q000628:therapy*; D001158:Arteries / Q000254:growth & development / Q000473:pathology / Q000648:ultrastructure; D003327:Coronary Disease / Q000473:pathology / Q000628:therapy*; D003331:Coronary Vessels / Q000254:growth & development / Q000473:pathology; D015870:Gene Expression; D005822:Genetic Vectors; D007269:Injections, Intra-Arterial; D008081:Liposomes / Q000008:administration & dosage; D016491:Peripheral Vascular Diseases / Q000628:therapy; D010957:Plasmids; D013552:Swine; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics*
D042501:Angiogenic Proteins; D008081:Liposomes; D042461:Vascular Endothelial Growth Factor A