In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome

Yuichiro Saito, Tetsuya Nakamura, Yoshio Ohyama, Toru Suzuki, Akihiro Iida, Takako Shiraki-Iida, Makoto Kuro-o, Yo ichi Nabeshima, Masahiko Kurabayashi, Ryozo Nagai

Research output: Contribution to journalArticle

175 Scopus citations

Abstract

The klotho gene, originally identified by insertional mutagenesis in mice, suppresses multiple aging phenotypes (e.g., arteriosclerosis, pulmonary emphysema, osteoporosis, infertility, and short life span). We have previously shown that mice heterozygous for a defect in the klotho gene upon parabiosis with wild-type mice show improved endothelial function, suggesting that the klotho gene product protects against endothelial dysfunction. In the present study, using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat which demonstrates multiple atherogenic risk factors (e.g., hypertension, obesity, severe hyperglycemia, and hypertriglyceridemia) and is thus considered an experimental animal model of atherosclerotic disease, we show that adenovirus-mediated klotho gene delivery can (1) ameliorate vascular endothelial dysfunction, (2) increase nitric oxide production, (3) reduce elevated blood pressure, and (4) prevent medial hypertrophy and perivascular fibrosis. Based on these findings, klotho gene delivery improves endothelial dysfunction through a pathway involving nitric oxide, and is involved in modulating vascular function (e.g., hypertension and vascular remodeling). Our findings establish the basis for the therapeutic potential of klotho gene delivery in atherosclerotic disease. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)767-772
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume276
Issue number2
DOIs
StatePublished - Sep 24 2000

    Fingerprint

Keywords

  • Atherosclerosis
  • Diabetes mellitus
  • Endothelium
  • Gene therapy
  • Hyperlipidemia
  • Hypertension
  • Klotho
  • Nitric oxide
  • Obesity
  • Vascular remodeling

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Saito, Y., Nakamura, T., Ohyama, Y., Suzuki, T., Iida, A., Shiraki-Iida, T., Kuro-o, M., Nabeshima, Y. I., Kurabayashi, M., & Nagai, R. (2000). In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome. Biochemical and Biophysical Research Communications, 276(2), 767-772. https://doi.org/10.1006/bbrc.2000.3470