• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to project page

2013 Fiscal Year Final Research Report

Development of increasing functional HDL-C using antisense oligonucleotides as innovative therapy

Research Project

  • PDF
Project/Area Number 23591109
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Circulatory organs internal medicine
Research InstitutionNational Cardiovascular Center Research Institute

Principal Investigator

IWAMOTO Noriyuki  独立行政法人国立循環器病研究センター, 研究所, 客員研究員 (70534709)

Project Period (FY) 2011 – 2013
KeywordsHDL / ABCA1 / 核酸医薬
Research Abstract

The objective of this basic research is to analyze whether or not innovative antisense oligonucleotides targeted specific molecular gene would be candidate of increasing serum HDL-cholesterollevel through the ABCA1/apoA-I pathway. We previously demonstrated that transcription factor AP-2 negatively regulates the ATP-binding cassette A1 (ABCA1) gene through its Ser-phosphorylation by protein kinase PKD which is a common modulator of the DNA binding activity of AP-2 through their phosphorylation for negative regulation of the ABCA in genes expression. The Antisense oligoniculeotide modified BNA is so innovative that have stronger effective compared to previous one.
In this study, we demonstrated that the PKD specific targeted antisense could increase ABCA1 mRNA levels in liver in vitro and in vivo, which result in raising serum HDL-C level in vivo. To further develop this strategy, we need more experiments to figure out the value of efficacy and safety using oligonucleotides therapy

  • Research Products

    (3 results)

All 2011 2008 2007

All Journal Article (3 results) (of which Peer Reviewed: 3 results)

  • [Journal Article] Protein kinase D regulates the adiponectin gene expression through phosphorylation of AP-2: a common pathway to the ABCA1 gene regulation2011

    • Author(s)
      Iwamoto N, Yokoyama S
    • Journal Title

      Atherosclerosis

      Volume: 216(1) Pages: 90-6

    • Peer Reviewed
  • [Journal Article] Involvement of protein kinase D in phosphorylation and increase of DNA binding of activator protein 2 alpha to downregulate ATP-binding cassette transporter A12008

    • Author(s)
      Iwamoto N, Abe-Dohmae S, Lu R, Yokoyama S
    • Journal Title

      Arterioscler Thromb Vasc Biol

      Volume: 28(12) Pages: 2282-7

    • Peer Reviewed
  • [Journal Article] ATP-binding cassette transporter A1 gene transcription is downregulated by activator protein 2alpha. Doxazosin inhibits activator protein 2alpha and increases high-density lipoprotein biogenesis independent of alpha1-adrenoceptor blockade2007

    • Author(s)
      Iwamoto N, Abe-Dohmae S, Ayaori M, Tanaka N, Kusuhara M, Ohsuzu F, Yokoyama S
    • Journal Title

      Circ Res

      Volume: 20;101(2) Pages: 156-65

    • Peer Reviewed

URL: 

Published: 2015-07-16  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi