Effects of PDGF A-chain antisense oligodeoxynucleotides on growth of cardiovascular organs in stroke-prone spontaneously hypertensive rats.
We examined the effects of the platelet-derived growth factor (PDGF) A-chain antisense oligodeoxynucleotides (ODN) on cardiovascular organ growth in stroke-prone spontaneously hypertensive rats (SHR-SP) in vivo. Expression of PDGF A-chain mRNA was higher in the aorta and kidney in 9-week-old SHR-SP than in Wistar-Kyoto (WKY) rats. A phosphorothioate-linked 15-mer antisense ODN complementary to the initiation codon region of rat PDGF A-chain mRNA and a control sense ODN were infused subcutaneously into SHR-SP/Izumo at a dose of 90 ng/g body weight/day for 28 days using an implanted ALZET pump. The PDGF A-chain antisense ODN did not affect blood pressure or body weight. The antisense ODN significantly inhibited [3H]thymidine incorporation into the DNA in the aorta and kidney but not in the heart. Infusion of the antisense ODN considerably reduced production of PDGF A-chain protein but did not affect expression of PDGF A-chain mRNA. Infusion of the antisense ODN considerably improved the arterial and renal tissue damage in SHR-SP morphologically. From these findings, it can be confirmed that suppression of PDGF A-chain by the antisense DNA is useful as a gene therapy for treating cardiovascular organ damage in hypertension.
Kishioka
H
H
Department of Internal Medicine, Nihon University School of Medicine, Tokyo, Japan.
Fukuda
N
N
Wen-Yang
H
H
Nakayama
M
M
Watanabe
Y
Y
Kanmatsuse
K
K
D000818:Animals; D015153:Blotting, Western; D002319:Cardiovascular System / Q000187:drug effects* / Q000254:growth & development* / Q000473:pathology; D004195:Disease Models, Animal; D006973:Hypertension / Q000235:genetics / Q000473:pathology*; D007668:Kidney / Q000187:drug effects / Q000254:growth & development / Q000473:pathology; D008297:Male; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020521:Stroke / Q000235:genetics / Q000473:pathology*
D020319:Oligodeoxyribonucleotides, Antisense; D010982:Platelet-Derived Growth Factor; C075278:platelet-derived growth factor A