Abstract：
UNASSIGNED: Fibroblast growth factor 21 (FGF21) has a protective effect against cardiovascular disease. However, the role of FGF21 in hypertension remains elusive.
UNASSIGNED: Ten-week-old male C57BL/6 mice were randomly divided into normal-salt (NS) group, NS+FGF21 group, deoxycorticosterone acetate-salt (DOCA) group and DOCA+FGF21 group. The mice in NS group underwent uninephrectomy without receiving DOCA and 1% NaCl and the mice in DOCA group were subjected to uninephrectomy and DOCA-salt (DOCA and 1% NaCl) treatment for 6 weeks. At the same time, the mice were infused with vehicle (artificial cerebrospinal fluid, aCSF) or FGF21 (1 mg/kg) into the bilateral paraventricular nucleus (PVN) of mice.
UNASSIGNED: Here, we showed that FGF21 treatment lowered DOCA salt-induced inflammation and oxidative stress in the PVN, which reduced sympathetic nerve activity and hypertension. Mechanistically, FGF21 treatment decreased the expression of HNF4α and inhibited the binding activity of HNF4α to the promoter region of ACE2 in the PVN of DOCA salt-treated mice, which further up-regulated ACE2/Ang (1-7) signals in the PVN. In addition, ACE2 deficiency abolished the protective effect of FGF21 in DOCA salt-treated mice, suggesting that FGF21-mediated antihypertensive effect was dependent on ACE2.
UNASSIGNED: The results demonstrate that FGF21 protects against salt-sensitive hypertension via regulating HNF4α/ACE2/Ang (1-7) axis in the PVN of DOCA salt-treated mice via multi-organ crosstalk between liver, brain and blood vessels.
UNASSIGNED: Ten-week-old male C57BL/6 mice were randomly divided into normal-salt (NS) group, NS+FGF21 group, deoxycorticosterone acetate-salt (DOCA) group and DOCA+FGF21 group. The mice in NS group underwent uninephrectomy without receiving DOCA and 1% NaCl and the mice in DOCA group were subjected to uninephrectomy and DOCA-salt (DOCA and 1% NaCl) treatment for 6 weeks. At the same time, the mice were infused with vehicle (artificial cerebrospinal fluid, aCSF) or FGF21 (1 mg/kg) into the bilateral paraventricular nucleus (PVN) of mice.
UNASSIGNED: Here, we showed that FGF21 treatment lowered DOCA salt-induced inflammation and oxidative stress in the PVN, which reduced sympathetic nerve activity and hypertension. Mechanistically, FGF21 treatment decreased the expression of HNF4α and inhibited the binding activity of HNF4α to the promoter region of ACE2 in the PVN of DOCA salt-treated mice, which further up-regulated ACE2/Ang (1-7) signals in the PVN. In addition, ACE2 deficiency abolished the protective effect of FGF21 in DOCA salt-treated mice, suggesting that FGF21-mediated antihypertensive effect was dependent on ACE2.
UNASSIGNED: The results demonstrate that FGF21 protects against salt-sensitive hypertension via regulating HNF4α/ACE2/Ang (1-7) axis in the PVN of DOCA salt-treated mice via multi-organ crosstalk between liver, brain and blood vessels.
摘要：
■成纤维细胞生长因子21（FGF21）对心血管疾病具有保护作用。然而,FGF21在高血压中的作用仍然难以捉摸.
■将10周龄雄性C57BL/6小鼠随机分为正常盐（NS）组，NS+FGF21组,脱氧皮质酮乙酸盐（DOCA）组和DOCA+FGF21组。NS组的小鼠在不接受DOCA和1％NaCl的情况下进行单肾切除术，DOCA组的小鼠进行单肾切除术和DOCA盐（DOCA和1％NaCl）治疗6周。同时,小鼠被注入媒介物(人工脑脊液，aCSF）或FGF21（1mg/kg）进入小鼠的双侧室旁核（PVN）。
■这里，我们发现FGF21治疗可降低DOCA盐诱导的PVN炎症和氧化应激，减少交感神经活动和高血压。机械上,FGF21处理降低了DOCA盐处理小鼠PVN中HNF4α的表达,抑制了HNF4α与ACE2启动子区的结合活性,其进一步上调PVN中的ACE2/Ang(1-7)信号。此外,ACE2缺乏消除了FGF21在DOCA盐处理小鼠中的保护作用，提示FGF21介导的抗高血压作用依赖于ACE2.
■结果表明，FGF21通过调节DOCA盐处理小鼠PVN中的HNF4α/ACE2/Ang（1-7）轴，通过肝脏之间的多器官串扰，大脑和血管.
■将10周龄雄性C57BL/6小鼠随机分为正常盐（NS）组，NS+FGF21组,脱氧皮质酮乙酸盐（DOCA）组和DOCA+FGF21组。NS组的小鼠在不接受DOCA和1％NaCl的情况下进行单肾切除术，DOCA组的小鼠进行单肾切除术和DOCA盐（DOCA和1％NaCl）治疗6周。同时,小鼠被注入媒介物(人工脑脊液，aCSF）或FGF21（1mg/kg）进入小鼠的双侧室旁核（PVN）。
■这里，我们发现FGF21治疗可降低DOCA盐诱导的PVN炎症和氧化应激，减少交感神经活动和高血压。机械上,FGF21处理降低了DOCA盐处理小鼠PVN中HNF4α的表达,抑制了HNF4α与ACE2启动子区的结合活性,其进一步上调PVN中的ACE2/Ang(1-7)信号。此外,ACE2缺乏消除了FGF21在DOCA盐处理小鼠中的保护作用，提示FGF21介导的抗高血压作用依赖于ACE2.
■结果表明，FGF21通过调节DOCA盐处理小鼠PVN中的HNF4α/ACE2/Ang（1-7）轴，通过肝脏之间的多器官串扰，大脑和血管.
