Suppr
超能文献

寻找肺动脉高压的治疗方法：17β-雌二醇对人肺动脉 PGI 通路的影响。

In search of pulmonary hypertension treatments: Effect of 17β-estradiol on PGI pathway in human pulmonary artery.

机构信息

Université de Paris, INSERM, UMR-S 1148, CHU X. Bichat, 75018 Paris, France; Université Sorbonne Paris Nord, 93430 Villetaneuse, France.

Alexandria University, Faculty of Pharmacy, Department of Pharmacology and Toxicology, Alexandria, Egypt; Arab Academy for Science, Technology & Maritime Transport, College of Pharmacy, Alexandria, Egypt.

出版信息

Prostaglandins Leukot Essent Fatty Acids. 2021 Sep;172:102321. doi: 10.1016/j.plefa.2021.102321. Epub 2021 Aug 9.

DOI:10.1016/j.plefa.2021.102321

PMID:34403986

Abstract

INTRODUCTION

Prostacyclin (PGI) is synthetized by PGI synthase (PGIS) and induces vasorelaxation via activation of cyclic AMP (cAMP) generating IP-receptor. Several components of the PGI signaling pathway are reduced in patients with pulmonary hypertension (PH).

AIM

To study the effect of 17β-estradiol (E2) on the PGI signaling pathway in human pulmonary arteries (HPA) and in their smooth muscle cells (hPASMC) derived from Group-3 PH and non-PH patients.

METHODS

Following E2-treatments of isolated HPA and cultured hPASMC, we measured: 6-keto-Prostaglandin F (PGI stable metabolite) by ELISA, PGIS and IP protein levels by Western blot and HPA vasorelaxations with an organ bath system.

RESULTS

Incubation with E2 (24/48 h, doses ≥ 10 nM) significantly increased the expression of PGIS in hPASMC derived from both PH (65-98%) and non-PH (21-33%) patients, whereas incubation with E2 (2 h, 0.1 and 1 µM) increased 6-keto-PGF production in HPA from Group-3 PH patients only, and did not affect 6-keto-PGF production in hPASMC from either non-PH or Group-3 PH patients. Increases in IP receptor expression were observed following 10 mM E2-treatment of hPASMC from non-PH (33% after 48 h) and Group-3 PH (23% after 24 h) patient lungs. Finally, preincubation with 100 nM E2 significantly increased arachidonic acid-induced vasorelaxation of HPA from non-PH patient lungs but not of HPA from Group-3 PH patient lungs.

CONCLUSION

E2-treatment may help to restore the PGI-pathway in Group-3 PH.

摘要

简介

前列环素（PGI）由 PGI 合酶（PGIS）合成，并通过激活环磷酸腺苷（cAMP）生成 IP 受体诱导血管舒张。肺动脉高压（PH）患者的 PGI 信号通路的几个组成部分减少。

目的

研究 17β-雌二醇（E2）对来自 PH 组 3 和非 PH 患者的人肺动脉（HPA）及其平滑肌细胞（hPASMC）中 PGI 信号通路的影响。

方法

在分离的 HPA 和培养的 hPASMC 进行 E2 处理后，我们测量了：ELISA 法测定 6-酮-PGF（PGI 稳定代谢物）、Western blot 法测定 PGIS 和 IP 蛋白水平以及器官浴系统测定 HPA 血管舒张。

结果

E2（24/48 小时，剂量≥10 nM）孵育显著增加了来自 PH（65-98%）和非 PH（21-33%）患者的 hPASMC 中 PGIS 的表达，而 E2（2 小时，0.1 和 1 μM）孵育仅增加了来自 PH 组 3 患者的 HPA 中 6-酮-PGF 的产生，并且不影响来自非 PH 或 PH 组 3 患者的 hPASMC 中 6-酮-PGF 的产生。在非 PH（48 小时后 33%）和 PH 组 3（24 小时后 23%）患者的 hPASMC 中，用 10 mM E2 处理后观察到 IP 受体表达增加。最后，用 100 nM E2 预孵育可显著增加非 PH 患者肺 HPA 中花生四烯酸诱导的血管舒张，但不能增加 PH 组 3 患者肺 HPA 的血管舒张。