Protective role of endothelial progenitor cells stimulated by riociguat in chronic thromboembolic pulmonary hypertension
Protective role of endothelial progenitor cells stimulated by riociguat in chronic thromboembolic pulmonary hypertension
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利奥西呱刺激内皮祖细胞对慢性血栓栓塞性肺动脉高压的保护作用
DOI：
10.1016/j.ijcard.2019.07.017
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发表时间：
2020
影响因子：
3.5
通讯作者：
Tatsumi Koichiro
中科院分区：
文献类型：
--
作者：
Yamamoto Keiko;Nishimura Rintaro;Kato Fumiaki;Naito Akira;Suda Rika;Sekine Ayumi;Jujo Takayuki;Shigeta Ayako;Sakao Seiichiro;Tanabe Nobuhiro;Tatsumi Koichiro
研究背景肺内皮损伤对维持正常肺血管功能产生负面影响。这种损伤导致慢性血栓栓塞性肺动脉高压（CTEPH）中血栓溶解延迟和血管重塑。尽管内皮祖细胞（EPC）可能在血管修复过程中融入新血管系统，但它们在 CTEPH 中的功能仍不清楚，特别是在可溶性鸟苷酸环化酶（sGC）活性增强的情况下。 方法和结果我们评估了 EPC 对内皮功能的影响，并比较了 sGC 刺激剂利奥西呱对循环细胞数量和功能的影响。 两组 CTEPH 患者的 EPC。两组包括 16 名未接受过治疗的 CTEPH 患者（未接受治疗组）和 14 名正在接受 sGC 刺激剂利奥西呱治疗的 CTEPH 患者（利奥西呱组）。 Riociguat 组的循环 EPC 数量显着高于 Naïve 组。 Riociguat 组的 EPC 中与血管生成相关的基因表达水平显着较高。 Riociguat 组中 EPC 刺激的人肺微血管内皮细胞 (hPMVEC) 管形成和迁移超过 Naïve 组。与 sGC 刺激剂 BAY 41-2272 相比，利奥西呱组中 EPC 刺激的 hPMVEC 的血管生成能力增强。结论这些研究结果表明，利奥西呱可能通过调节与 CTEPH 相关的内皮功能来诱导 EPC 发挥保护作用。工作的翻译方面内皮功能障碍加剧 CTEPH。利奥西呱通过新生血管形成增强 EPC 的保护作用，从而防止血管重塑并缓解 CTEPH。
BackgroundPulmonary endothelial damage has a negative impact on the maintenance of normal pulmonary vascular function. Such damage results in delayed thrombus dissolution and vascular remodeling in chronic thromboembolic pulmonary hypertension (CTEPH). Although endothelial progenitor cells (EPCs) may be incorporated into neovasculature during vascular repair, their function in CTEPH remains unclarified, especially under the augmentation of soluble guanylate cyclase (sGC) activity.Methods and resultsWe evaluated the effect of EPCs on endothelial function and compared the effect of riociguat, a sGC stimulator, on the number and function of circulating EPCs in two groups of CTEPH patients. The two groups consisted 16 CTEPH patients who were treatment naïve (Naïve group), and 14 CTEPH patients who were being treated with riociguat, a sGC stimulator (Riociguat group). The number of circulating EPCs in the Riociguat group was significantly higher than that in the Naïve group. Gene expression levels associated with angiogenesis were significantly higher in EPCs of the Riociguat group. EPC-stimulated tube formation and migration of human pulmonary microvascular endothelial cell (hPMVEC) in the Riociguat group exceeded that in the Naïve group. The angiogenic ability of hPMVECs stimulated by EPCs in the Riociguat group was enhanced compared to that of the sGC stimulator, BAY 41–2272.ConclusionThese findings indicate that riociguat may induce EPCs to play a protective role via modulation of endothelial functions associated with CTEPH.Translation aspect of the workEndothelial dysfunction exacerbates CTEPH. Riociguat enhanced the protective role of EPCs via neovascularization, which prevented vascular remodeling and alleviated CTEPH.