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

171 Citations (Scopus)

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

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Genes
Blood Vessels
Nitric Oxide
Parabiosis
Inbred OLETF Rats
Hypertension
Pulmonary Emphysema
Mutagenesis
Morbid Obesity
Arteriosclerosis
Hypertriglyceridemia
Insertional Mutagenesis
Blood pressure
Adenoviridae
Hyperglycemia
Infertility
Hypertrophy
Osteoporosis
Rats
Animals

Keywords

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

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome. / Saito, Yuichiro; Nakamura, Tetsuya; Ohyama, Yoshio; Suzuki, Toru; Iida, Akihiro; Shiraki-Iida, Takako; Kuro-o, Makoto; Nabeshima, Yo ichi; Kurabayashi, Masahiko; Nagai, Ryozo.

In: Biochemical and Biophysical Research Communications, Vol. 276, No. 2, 24.09.2000, p. 767-772.

Research output: Contribution to journalArticle

Saito, Y, Nakamura, T, Ohyama, Y, Suzuki, T, Iida, A, Shiraki-Iida, T, Kuro-o, M, Nabeshima, YI, Kurabayashi, M & Nagai, R 2000, 'In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome', Biochemical and Biophysical Research Communications, vol. 276, no. 2, pp. 767-772. https://doi.org/10.1006/bbrc.2000.3470
Saito, Yuichiro ; Nakamura, Tetsuya ; Ohyama, Yoshio ; Suzuki, Toru ; Iida, Akihiro ; Shiraki-Iida, Takako ; Kuro-o, Makoto ; Nabeshima, Yo ichi ; Kurabayashi, Masahiko ; Nagai, Ryozo. / In vivo klotho gene delivery protects against endothelial dysfunction in multiple risk factor syndrome. In: Biochemical and Biophysical Research Communications. 2000 ; Vol. 276, No. 2. pp. 767-772.
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