Department of Neurosurgery, Ganzhou Hospital of Guangdong Provincial People's Hospital, Ganzhou Municipal Hospital, Ganzhou, Jiangxi, China.
Department of Neurosurgery, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China.
Clin Exp Hypertens. 2023 Dec 31;45(1):2277654. doi: 10.1080/10641963.2023.2277654. Epub 2023 Nov 14.
Endothelial dysfunction is a critical initiating factor in the development of hypertension and related complications. Follistatin-like 1 (FSTL1) can promote endothelial cell function and stimulates revascularization in response to ischemic insult. However, it is unclear whether FSTL1 has an effect on ameliorating endothelial dysfunction in spontaneously hypertensive rats (SHRs).
Wistar Kyoto (WKY) and SHRs were treated with a tail vein injection of vehicle (1 mL/day) or recombinant FSTL1 (100 μg/kg body weight/day) for 4 weeks. Blood pressure was measured by tail-cuff plethysmograph, and vascular reactivity in mesenteric arteries was measured using wire myography.
We found that treatment with FSTL1 reversed impaired endothelium-dependent relaxation (EDR) in mesenteric arteries and lowered blood pressure of SHRs. Decreased AMP-activated protein kinase (AMPK) phosphorylation, elevated endoplasmic reticulum (ER) stress markers, increased reactive oxygen species (ROS), and reduction of nitric oxide (NO) production in mesenteric arteries of SHRs were also reversed by FSTL1 treatment. treatment with FSTL1 improved the impaired EDR in mesenteric arteries from SHRs and reversed tunicamycin (ER stress inducer)-induced ER stress and the impairment of EDR in mesenteric arteries from WKY rats. The effects of FSTL1 were abolished by cotreatment of compound C (AMPK inhibitor).
These results suggest that FSTL1 prevents endothelial dysfunction in mesenteric arteries of SHRs through inhibiting ER stress and ROS and increasing NO production via activation of AMPK signaling.
内皮功能障碍是高血压及其相关并发症发展的关键起始因素。卵泡抑素样 1（Follistatin-like 1，FSTL1）可促进内皮细胞功能，并在缺血损伤时刺激血管再生。然而，FSTL1 是否对改善自发性高血压大鼠（Spontaneously hypertensive rats，SHRs）的内皮功能障碍尚不清楚。
用尾静脉注射载体（1ml/天）或重组 FSTL1（100μg/kg 体重/天）对 Wistar Kyoto（WKY）和 SHRs 进行 4 周处理。通过尾套测压法测量血压，通过线描法测量肠系膜动脉的血管反应性。
我们发现，FSTL1 治疗可逆转肠系膜动脉内皮依赖性舒张（endothelium-dependent relaxation，EDR）受损，并降低 SHRs 的血压。SHRs 肠系膜动脉中 AMP 激活蛋白激酶（AMP-activated protein kinase，AMPK）磷酸化减少、内质网（endoplasmic reticulum，ER）应激标志物升高、活性氧（reactive oxygen species，ROS）增加和一氧化氮（nitric oxide，NO）生成减少也被 FSTL1 治疗所逆转。FSTL1 治疗还改善了 SHRs 肠系膜动脉中受损的 EDR，并逆转了衣霉素（内质网应激诱导剂）诱导的 WKY 大鼠肠系膜动脉 ER 应激和 EDR 损伤。用化合物 C（AMPK 抑制剂）共同处理可消除 FSTL1 的作用。
这些结果表明，FSTL1 通过抑制 ER 应激和 ROS 并增加 NO 生成来激活 AMPK 信号通路，从而防止 SHRs 肠系膜动脉的内皮功能障碍。
