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. 2020 Jan 15:299:263-270.
doi: 10.1016/j.ijcard.2019.07.017. Epub 2019 Jul 15.

Protective role of endothelial progenitor cells stimulated by riociguat in chronic thromboembolic pulmonary hypertension

Keiko Yamamoto  1 , Rintaro Nishimura  2 , Fumiaki Kato  3 , Akira Naito  2 , Rika Suda  2 , Ayumi Sekine  2 , Takayuki Jujo  2 , Ayako Shigeta  2 , Seiichiro Sakao  2 , Nobuhiro Tanabe  2 , Koichiro Tatsumi  2
Affiliations
Free article

Protective role of endothelial progenitor cells stimulated by riociguat in chronic thromboembolic pulmonary hypertension

Keiko Yamamoto et al. Int J Cardiol. .
Free article

Abstract

Background: 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.

Methods and results: 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.

Conclusion: These findings indicate that riociguat may induce EPCs to play a protective role via modulation of endothelial functions associated with CTEPH.

Translation aspect of the work: Endothelial dysfunction exacerbates CTEPH. Riociguat enhanced the protective role of EPCs via neovascularization, which prevented vascular remodeling and alleviated CTEPH.

Keywords: Angiogenesis; Chronic thromboembolic pulmonary hypertension; Endothelial progenitor cells; Soluble guanylate cyclase.

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Comment in

  • Effect of riociguat from a different angle.
    Sugimura K. Sugimura K. Int J Cardiol. 2020 Apr 1;304:156-157. doi: 10.1016/j.ijcard.2019.12.017. Epub 2019 Dec 16. Int J Cardiol. 2020. PMID: 31882359 No abstract available.
  • Reply to letter to Editor.
    Yamamoto K, Nishimura R, Kato F, Naito A, Suda R, Sekine A, Jujo T, Shigeta A, Sakao S, Tanabe N, Tatsumi K. Yamamoto K, et al. Int J Cardiol. 2020 May 15;307:164. doi: 10.1016/j.ijcard.2020.03.015. Int J Cardiol. 2020. PMID: 32354405 No abstract available.
  • EPC modulation, a new mechanism for CTEPH therapy?
    Chen L, Liu C, Tang R, Xu J, Zhang N, Wang J, Lu W, Wang T. Chen L, et al. Int J Cardiol. 2020 May 15;307:165. doi: 10.1016/j.ijcard.2020.02.021. Int J Cardiol. 2020. PMID: 32354406 No abstract available.

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