Widespread regional myocardial transfection by plasmid encoding Del-1 following retrograde coronary venous delivery.
This study quantifies myocardial transfection following percutaneous retrograde coronary venous delivery (RCVD) of a plasmid encoding human Del-1. RCVD of Del-1, GFP plasmid, or marker dye was conducted in 14 pigs. After selective cannulation of a coronary vein, a delivery site was confirmed by contrast injection and myocardial blush. Ten milliliters of plasmid hDel-1 or GFP was administered. Animals were euthanized 3 and 7 days post-RCVD. hDel-1 gene expression was evaluated by quantitative RT-PCR. An average myocardial expression of 4.5 x 10(5) copies hDel-1/microg total RNA was observed within the approximately 5 x 5 cm(2) target tissue of the left ventricle. GFP expression was detected by fluorescent microscopy. hDel-1 protein expression was confirmed by immunohistochemistry. Regionalized myocardial expression was found in all pigs. hDel-1 RNA was not found in distant tissues except in the three pigs with prominent venovenous washout (PVW). These levels were 3 to 4 log unites lower than those found in myocardium. Single retrograde coronary venous administration resulted in efficient regional myocyte transfection of hDel-1 and GFP. This method may be useful and clinically feasible for myocardial angiogenesis therapy.
Hou
Dongming
D
Indiana University School of Medicine, Indianapolis, Indiana, USA.
Maclaughlin
Fiona
F
Thiesse
Mary
M
Panchal
Vipul R
VR
Bekkers
Bas C A M
BC
Wilson
Elizabeth A
EA
Rogers
Pamela I
PI
Coleman
Michael C
MC
March
Keith L
KL
D000818:Animals; D002135:Calcium-Binding Proteins; D006328:Cardiac Catheterization; D002352:Carrier Proteins / Q000235:genetics*; D015815:Cell Adhesion Molecules; D016503:Drug Delivery Systems; D018014:Gene Transfer Techniques; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D008164:Luminescent Proteins; D009206:Myocardium / Q000378:metabolism*; D010957:Plasmids; D013552:Swine; D014162:Transfection
D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C110183:EDIL3 protein, human; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins