Department of Anesthesiology, Second Xiangya Hospital, Changsha, PR China.
Pharmacology. 2012;90(5-6):342-7. doi: 10.1159/000338754. Epub 2012 Oct 19.
BACKGROUND/AIMS: Propofol, a widely used sedative-hypnotic agent for induction/maintenance of anesthesia and sedation of critically ill patients, reportedly has therapeutic potential for hypertension. Angiotensin-converting enzyme 2 (ACE2) is a promising therapeutic target for pulmonary arterial hypertension. In the present study, we explored the effect of propofol on ACE2 expression in human pulmonary artery endothelial cells (HPAECs).
HPAECs were treated with propofol in different concentrations (1, 10, 20, 40 or 50 µmol/l) for different lengths of time (6, 12, 18, 24 or 30 h) with or without transcription inhibitor actinomycin D or phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002.
Propofol increased the ACE2 mRNA level in a dose- and time-dependent manner within 24 h. Propofol treatment dose-dependently increased the ACE2 protein level and the cell membrane ACE2 activity. Transcription inhibitor actinomycin D and PI3K inhibitor LY294002 abrogated the augmenting effect of propofol on the mRNA level of ACE2 in HPAECs.
Propofol enhances the ACE2 expression in HPAECs by increasing the transcription of ACE2 via a PI3K-dependent mechanism, which leads to increased ACE2 activity on the cell membrane. This study provides new insights into propofol's vascular protective effects as well as its therapeutic potential for pulmonary arterial hypertension.
背景/目的：丙泊酚是一种广泛用于诱导/维持麻醉和镇静危重病患者的镇静催眠药物，据报道对高血压具有治疗潜力。血管紧张素转换酶 2（ACE2）是肺动脉高压的有前途的治疗靶点。在本研究中，我们探讨了丙泊酚对人肺动脉内皮细胞（HPAEC）中 ACE2 表达的影响。
用不同浓度（1、10、20、40 或 50μmol/l）的丙泊酚处理 HPAEC 不同时间（6、12、18、24 或 30h），并用或不用转录抑制剂放线菌素 D 或磷脂酰肌醇 3-激酶（PI3K）抑制剂 LY294002。
丙泊酚在 24 小时内以剂量和时间依赖的方式增加 ACE2 mRNA 水平。丙泊酚处理剂量依赖性地增加 ACE2 蛋白水平和细胞膜 ACE2 活性。转录抑制剂放线菌素 D 和 PI3K 抑制剂 LY294002 阻断了丙泊酚对 HPAEC 中 ACE2 mRNA 水平的增强作用。
丙泊酚通过增加 ACE2 的转录，通过 PI3K 依赖性机制增强 HPAEC 中的 ACE2 表达，导致细胞膜上 ACE2 活性增加。这项研究为丙泊酚的血管保护作用及其治疗肺动脉高压的潜在治疗作用提供了新的见解。
