title: Widespread regional myocardial transfection by plasmid encoding Del-1 following retrograde coronary venous delivery.
abstract: 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.
authors.affiliation: Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Dongming
authors.initials: D
authors.lastname: Hou
authors.forename: Fiona
authors.initials: F
authors.lastname: Maclaughlin
authors.forename: Mary
authors.initials: M
authors.lastname: Thiesse
authors.forename: Vipul R
authors.initials: VR
authors.lastname: Panchal
authors.forename: Bas C A M
authors.initials: BC
authors.lastname: Bekkers
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Wilson
authors.forename: Pamela I
authors.initials: PI
authors.lastname: Rogers
authors.forename: Michael C
authors.initials: MC
authors.lastname: Coleman
authors.forename: Keith L
authors.initials: KL
authors.lastname: March
mesh_terms: 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
chemical_list: D002135:Calcium-Binding Proteins; D002352:Carrier Proteins; D015815:Cell Adhesion Molecules; C110183:EDIL3 protein, human; D008164:Luminescent Proteins; D049452:Green Fluorescent Proteins