Effects of PDGF A-chain antisense oligodeoxynucleotides on growth of cardiovascular organs in stroke-prone spontaneously hypertensive rats

  • Kishioka H
  • Fukuda N
  • Wen-Yang H
 et al. 
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Abstract

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. © 2001 American Journal of Hypertension, Ltd.

Author-supplied keywords

  • Antisense DNA
  • Gene therapy
  • Platelet-derived growth factor
  • Stroke-prone spontaneously hypertensive rat

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Authors

  • Hirobumi Kishioka

  • Noboru Fukuda

  • Hu Wen-Yang

  • Mari Nakayama

  • Yoshiyasu Watanabe

  • Katsuo Kanmatsuse

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