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 (Klf5^PostnKO: 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^PostnKO 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.