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

Influence of periostin-positive cell-specific Klf5 deletion on aortic thickening in DOCA-salt hypertensive mice.
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DOI:
10.1038/hr.2016.65
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发表时间:
2016-11
期刊:
Hypertension research : official journal of the Japanese Society of Hypertension
影响因子:
--
通讯作者:
Nagai R
Nagai R
中科院分区:
其他
文献类型:
--
作者:
Zempo H;Suzuki JI;Ogawa M;Watanabe R;Fujiu K;Manabe I;Conway SJ;Taniyama Y;Morishita R;Hirata Y;Isobe M;Nagai R

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慢性高血压引起血管重构,这与骨膜蛋白(后n)阳性细胞的增加有关,包括成纤维细胞和平滑肌细胞。kr<s:1> pel样因子(KLF) 5是一种转录因子,在血管重构中也被观察到,然而,在醋酸脱氧皮质酮(DOCA)盐诱导的血管重构过程中,KLF5在n后阳性细胞中所起的作用尚不清楚。我们使用了postn阳性细胞特异性Klf5缺陷(Klf5PostnKO: Klf5flox/flox; postnre /−)小鼠和野生型(WT: Klf5flox/flox; postn−/−)小鼠。我们植入DOCA微球,并提供含0.9% NaCl的饮用水,持续8周。在两个基因型组中,doca盐治疗均诱导高血压,观察到收缩压升高。在WT中,与未治疗的对照组相比,doca盐治疗增加了主动脉内侧面积。同样,与对照组相比,经doca盐处理的WT小鼠的主动脉中Tgf1b过表达。免疫荧光染色显示,doca盐干预后,WT主动脉内侧区存在成纤维细胞特异性蛋白1 (FSP1)+-α平滑肌肌动蛋白(αSMA)+肌成纤维细胞。重要的是,在Klf5PostnKO动物中没有观察到这些变化。综上所述,本研究结果提示,KLF5在后n阳性细胞上的存在参与了doca -盐高血压引起的主动脉增厚的发病机制。
Chronic hypertension causes vascular remodeling that is associated with an increase of 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 (Klf5PostnKO: Klf5flox/flox;PostnCre/−) mice and wild type (WT: Klf5flox/flox;Postn−/−) mice. We implanted a DOCA pellet and provided drinking water that containing 0.9% NaCl for eight-weeks. The DOCA-salt treatment induced hypertension in both genotype groups, as observed by the increase in systolic blood pressure. In WT, DOCA-salt treatment increased the aortic medial area compared to non-treated controls. Similarly, Tgf1b was overexpressed in the aortas of DOCA-salt treated WT mice compared to controls. Immunofluorescence staining revealed that fibroblast specific protein 1 (FSP1)+-α smooth muscle actin (αSMA)+ myofibroblast exist in the medial area of WT aorta 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 on postn positive cells contributes to the pathogenesis of aortic thickening induced by DOCA-salt hypertension.
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