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

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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.

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Kishioka, H., Fukuda, N., Wen-Yang, H., Nakayama, M., Watanabe, Y., & Kanmatsuse, K. (2001). Effects of PDGF A-chain antisense oligodeoxynucleotides on growth of cardiovascular organs in stroke-prone spontaneously hypertensive rats. American Journal of Hypertension, 14(5 I), 439–445. https://doi.org/10.1016/S0895-7061(00)01290-5

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