Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice

Hirofumi Zempo, Jun Ichi Suzuki, Masahito Ogawa, Ryo Watanabe, Katsuhito Fujiu, Ichiro Manabe, Simon Conway, Yoshiaki Taniyama, Ryuichi Morishita, Yasunobu Hirata, Mitsuaki Isobe, Ryozo Nagai

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Abstract

Chronic hypertension causes vascular remodeling that is associated with an increase in periostin- (postn) positive cells, including fibroblasts and smooth muscle cells. Krüppel-like factor (KLF) 5, a transcription factor, is also observed in vascular remodeling; however, it is unknown what role KLF5 plays in postn-positive cells during vascular remodeling induced by deoxycorticosterone-acetate (DOCA) salt. We used postn-positive cell-specific Klf5-deficient mice (Klf5 Postn KO: Klf5 flox/flox; Postn Cre/-) and wild-type mice (WT: Klf5 flox/flox; Postn -/-). We implanted a DOCA pellet and provided drinking water containing 0.9% NaCl for 8 weeks. The DOCA-salt treatment induced hypertension in both genotypes, as observed by increases in systolic blood pressure. In WT animals, DOCA-salt treatment increased the aortic medial area compared with the non-treated controls. Similarly, Tgfb1 was overexpressed in the aortas of the DOCA-salt treated WT mice compared with the controls. Immunofluorescence staining revealed that fibroblast-specific protein 1 (FSP1) + -α smooth muscle actin (αSMA) + myofibroblasts exist in the medial area of the WT aortas after DOCA-salt intervention. Importantly, these changes were not observed in the Klf5 Postn KO animals. In conclusion, the results of this study suggest that the presence of KLF5 in postn-positive cells contributes to the pathogenesis of aortic thickening induced by DOCA-salt hypertension.

Original languageEnglish (US)
Pages (from-to)764-768
Number of pages5
JournalHypertension Research
Volume39
Issue number11
DOIs
StatePublished - Nov 1 2016

Fingerprint

Desoxycorticosterone
Acetates
Salts
Hypertension
Aorta
Blood Pressure
Myofibroblasts
Drinking Water
Smooth Muscle Myocytes
Fluorescent Antibody Technique
Smooth Muscle
Actins
Transcription Factors
Fibroblasts
Genotype
Staining and Labeling
Therapeutics

Keywords

  • deoxycorticosterone-acetate salt
  • Krüppel-like factor 5
  • periostin
  • remodeling

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Zempo, H., Suzuki, J. I., Ogawa, M., Watanabe, R., Fujiu, K., Manabe, I., ... Nagai, R. (2016). Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice. Hypertension Research, 39(11), 764-768. https://doi.org/10.1038/hr.2016.65

Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice. / Zempo, Hirofumi; Suzuki, Jun Ichi; Ogawa, Masahito; Watanabe, Ryo; Fujiu, Katsuhito; Manabe, Ichiro; Conway, Simon; Taniyama, Yoshiaki; Morishita, Ryuichi; Hirata, Yasunobu; Isobe, Mitsuaki; Nagai, Ryozo.

In: Hypertension Research, Vol. 39, No. 11, 01.11.2016, p. 764-768.

Research output: Contribution to journalArticle

Zempo, H, Suzuki, JI, Ogawa, M, Watanabe, R, Fujiu, K, Manabe, I, Conway, S, Taniyama, Y, Morishita, R, Hirata, Y, Isobe, M & Nagai, R 2016, 'Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice', Hypertension Research, vol. 39, no. 11, pp. 764-768. https://doi.org/10.1038/hr.2016.65
Zempo, Hirofumi ; Suzuki, Jun Ichi ; Ogawa, Masahito ; Watanabe, Ryo ; Fujiu, Katsuhito ; Manabe, Ichiro ; Conway, Simon ; Taniyama, Yoshiaki ; Morishita, Ryuichi ; Hirata, Yasunobu ; Isobe, Mitsuaki ; Nagai, Ryozo. / Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice. In: Hypertension Research. 2016 ; Vol. 39, No. 11. pp. 764-768.
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abstract = "Chronic hypertension causes vascular remodeling that is associated with an increase in periostin- (postn) positive cells, including fibroblasts and smooth muscle cells. Kr{\"u}ppel-like factor (KLF) 5, a transcription factor, is also observed in vascular remodeling; however, it is unknown what role KLF5 plays in postn-positive cells during vascular remodeling induced by deoxycorticosterone-acetate (DOCA) salt. We used postn-positive cell-specific Klf5-deficient mice (Klf5 Postn KO: Klf5 flox/flox; Postn Cre/-) and wild-type mice (WT: Klf5 flox/flox; Postn -/-). We implanted a DOCA pellet and provided drinking water containing 0.9{\%} NaCl for 8 weeks. The DOCA-salt treatment induced hypertension in both genotypes, as observed by increases in systolic blood pressure. In WT animals, DOCA-salt treatment increased the aortic medial area compared with the non-treated controls. Similarly, Tgfb1 was overexpressed in the aortas of the DOCA-salt treated WT mice compared with the controls. Immunofluorescence staining revealed that fibroblast-specific protein 1 (FSP1) + -α smooth muscle actin (αSMA) + myofibroblasts exist in the medial area of the WT aortas after DOCA-salt intervention. Importantly, these changes were not observed in the Klf5 Postn KO animals. In conclusion, the results of this study suggest that the presence of KLF5 in postn-positive cells contributes to the pathogenesis of aortic thickening induced by DOCA-salt hypertension.",
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AU - Fujiu, Katsuhito

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AU - Conway, Simon

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AU - Isobe, Mitsuaki

AU - Nagai, Ryozo

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AB - Chronic hypertension causes vascular remodeling that is associated with an increase in periostin- (postn) positive cells, including fibroblasts and smooth muscle cells. Krüppel-like factor (KLF) 5, a transcription factor, is also observed in vascular remodeling; however, it is unknown what role KLF5 plays in postn-positive cells during vascular remodeling induced by deoxycorticosterone-acetate (DOCA) salt. We used postn-positive cell-specific Klf5-deficient mice (Klf5 Postn KO: Klf5 flox/flox; Postn Cre/-) and wild-type mice (WT: Klf5 flox/flox; Postn -/-). We implanted a DOCA pellet and provided drinking water containing 0.9% NaCl for 8 weeks. The DOCA-salt treatment induced hypertension in both genotypes, as observed by increases in systolic blood pressure. In WT animals, DOCA-salt treatment increased the aortic medial area compared with the non-treated controls. Similarly, Tgfb1 was overexpressed in the aortas of the DOCA-salt treated WT mice compared with the controls. Immunofluorescence staining revealed that fibroblast-specific protein 1 (FSP1) + -α smooth muscle actin (αSMA) + myofibroblasts exist in the medial area of the WT aortas after DOCA-salt intervention. Importantly, these changes were not observed in the Klf5 Postn KO animals. In conclusion, the results of this study suggest that the presence of KLF5 in postn-positive cells contributes to the pathogenesis of aortic thickening induced by DOCA-salt hypertension.

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