Pressure-induced vector transport in human saphenous vein.
The efficiency of gene therapy as a pretreatment for saphenous vein coronary artery bypass grafts can be improved by increasing the transport of vector into the tunica media. The purpose of this study was to determine the effect of increasing transmural pressure on vector delivery depth in human saphenous vein segments. Specifically, we introduced adenovirus-sized microspheres luminally to observe changes in transport efficiency into the intimal and medial layers with increasing pressure. Our results indicate that transmural pressures of 100 and 400 mmHg increase the intimal concentration of microspheres as compared to 0 mmHg (p < 0.03), but do not significantly affect medial concentrations. We did not find increasing concentrations with increasing pressure above 100 mmHg. These results suggest that low or intermediate transmural pressures are adequate for intimal vector delivery and that techniques other than increasing pressure are required to deliver gene therapy vectors (> or = 100 nm) to medial smooth muscle cells. Also, our data support previous models designating the internal elastic lamina as the primary barrier to particle transport. Finally, our ex vivo microsphere perfusion experiment represents a novel way to explore functional vein permeabilities to gene therapy vectors and, ultimately, optimize vascular gene therapy protocols.
Ander
Sarah
S
Department of Biomedical Engineering, University of Wisconsin, Madison, WI 53706, USA.
MacLennan
Megan
M
Bentil
Sarah
S
Leavitt
Bruce
B
Chesler
Naomi
N
D000256:Adenoviridae / Q000235:genetics*; D001693:Biological Transport, Active / Q000502:physiology; D004279:DNA, Viral / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D018014:Gene Transfer Techniques; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D066298:In Vitro Techniques; D008863:Microspheres; D011312:Pressure; D012501:Saphenous Vein / Q000378:metabolism*; D014162:Transfection / Q000379:methods*
D004279:DNA, Viral