Effects of antisense peptide nucleic acid to platelet-derived growth factor A-chain on growth of vascular smooth muscle cells

Noboru Fukuda, Rie Furuya, Hirobumi Kishioka, Ryo Suzuki, Hiroyuki Matsuda, Yoshiko Tahira, Hiroto Takagi, Yukihiro Ikeda, Satoshi Saito, Koichi Matsumoto, Katsuo Kanmatsuse

Research output: Contribution to journalArticlepeer-review

5 Citations (Scopus)

Abstract

To investigate antisense peptide nucleic acid (PNA) as a gene therapy for the arterial proliferative diseases, the authors designed and examined the effects of an antisense PNA targeting platelet-derived growth factor (PDGF) A-chain on expression of PDGF A-chain and growth of vascular smooth muscle cells (VSMCs) from spontaneously hypertensive rats. A 15-mer antisense PNA complementary to the initiation codon of rat and human PDGF A-chain mRNA was synthesized and purified by high-performance liquid chromatography. Gel-shift assay and biomolecular interaction analysis (BIAcore) revealed that the antisense PNA bound weakly to the target RNA, whereas it bound strongly to the target DNA. Fluorescein-isothiocyanate-labeled antisense PNA to PDGF A-chain was taken up slowly and maintained in VSMCs for a prolonged period of time. Antisense PNA inhibited expression of PDGF A-chain mRNA and protein as well as DNA synthesis in VSMCs in a dose-independent manner. Inhibition of DNA synthesis by the antisense PNA was greater than that by the antisense DNA at a low concentration (0.5 μmol/L). These results suggest that antisense PNA to PDGF A-chain will be used as a gene therapy for vascular proliferative diseases such as hypertensive vascular diseases, restenosis of coronary arteries after angioplasty, and atherosclerosis.

Original languageEnglish
Pages (from-to)224-231
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume42
Issue number2
DOIs
Publication statusPublished - 1 Aug 2003

Keywords

  • Gene therapy
  • Growth
  • Peptide nucleic acid
  • Platelet-derived growth factor
  • Vascular smooth muscle

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