Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Department of Respirology, Graduate School of Medicine, Chiba University, Chiba 260-8670, Japan.
Int J Cardiol. 2020 Jan 15;299:263-270. doi: 10.1016/j.ijcard.2019.07.017. Epub 2019 Jul 15.
Pulmonary 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.
We 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.
These findings indicate that riociguat may induce EPCs to play a protective role via modulation of endothelial functions associated with CTEPH.
Endothelial dysfunction exacerbates CTEPH. Riociguat enhanced the protective role of EPCs via neovascularization, which prevented vascular remodeling and alleviated CTEPH.
肺血管内皮损伤会对维持正常的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）中血栓溶解和血管重构延迟。尽管内皮祖细胞（EPCs）在血管修复过程中可能被整合到新生血管中，但它们在 CTEPH 中的功能仍不清楚，尤其是在可溶性鸟苷酸环化酶（sGC）活性增强的情况下。
我们评估了 EPCs 对内皮功能的影响，并比较了 sGC 刺激剂 riociguat 在两组 CTEPH 患者中对循环 EPC 数量和功能的影响。两组患者分别为 16 例初治 CTEPH 患者（初治组）和 14 例接受 sGC 刺激剂 riociguat 治疗的 CTEPH 患者（Riociguat 组）。Riociguat 组的循环 EPC 数量明显高于初治组。Riociguat 组 EPC 中与血管生成相关的基因表达水平明显升高。Riociguat 组 EPC 刺激的人肺微血管内皮细胞（hPMVEC）管形成和迁移能力高于初治组。与 sGC 刺激剂 BAY 41-2272 相比，Riociguat 组 EPC 刺激的 hPMVEC 的血管生成能力增强。
这些发现表明，riociguat 可能通过调节与 CTEPH 相关的内皮功能诱导 EPCs 发挥保护作用。
内皮功能障碍加重 CTEPH。Riociguat 通过促进血管新生增强了 EPCs 的保护作用，从而防止血管重构并缓解 CTEPH。
