title: Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice.
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 (Klf5PostnKO: Klf5flox/flox; PostnCre/-) and wild-type mice (WT: Klf5flox/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 Klf5PostnKO 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.
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Zempo
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Jun-Ichi
authors.initials: JI
authors.lastname: Suzuki
authors.affiliation: Westmead Millennium Institute for Medical Research, Westmead, New South Wales, Australia.
authors.forename: Masahito
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Katsuhito
authors.initials: K
authors.lastname: Fujiu
authors.affiliation: Department of Cardiovascular Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Manabe
authors.affiliation: Developmental Biology and Neonatal Medicine Program, Herman B Wells Center for Pediatric Research, Indiana University of Medicine, Indianapolis, IN, USA.
authors.forename: Simon J
authors.initials: SJ
authors.lastname: Conway
authors.affiliation: Department of Clinical Gene Therapy, Osaka University, Osaka, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Taniyama
authors.affiliation: Department of Clinical Gene Therapy, Osaka University, Osaka, Japan.
authors.forename: Ryuichi
authors.initials: R
authors.lastname: Morishita
authors.affiliation: Department of Advanced Clinical Science and Therapeutics, The University of Tokyo, Tokyo, Japan.
authors.forename: Yasunobu
authors.initials: Y
authors.lastname: Hirata
authors.affiliation: Department of Cardiovascular Medicine, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Mitsuaki
authors.initials: M
authors.lastname: Isobe
authors.affiliation: Jichi Medical University, Shimotsuke City, Tochigi, Japan.
authors.forename: Ryozo
authors.initials: R
authors.lastname: Nagai
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism*; D001794:Blood Pressure / Q000502:physiology; D015815:Cell Adhesion Molecules / Q000378:metabolism*; D064791:Desoxycorticosterone Acetate; D006973:Hypertension / Q000139:chemically induced / Q000235:genetics* / Q000378:metabolism; D051741:Kruppel-Like Transcription Factors / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D058628:Myofibroblasts / Q000378:metabolism; D000071999:S100 Calcium-Binding Protein A4 / Q000235:genetics / Q000378:metabolism; D066253:Vascular Remodeling / Q000235:genetics*
chemical_list: D015815:Cell Adhesion Molecules; C118391:Klf5 protein, mouse; D051741:Kruppel-Like Transcription Factors; C082838:Postn protein, mouse; D000071999:S100 Calcium-Binding Protein A4; C470944:S100a4 protein, mouse; D064791:Desoxycorticosterone Acetate