Collagen triple helix repeat-containing protein 1 is a novel biomarker of right ventricular involvement in pulmonary hypertension

Tetsuro Yokokawa; Kazuto Nishiura; Masataka Katahira; Yu Sato; Shunsuke Miura; Akihiko Sato; Takeshi Shimizu; Tomofumi Misaka; Takamasa Sato; Takashi Kaneshiro; Masayoshi Oikawa; Akiomi Yoshihisa; Koichi Sugimoto; Kenji Fukushima; Kazuhiko Nakazato; Yasuchika Takeishi

doi:10.1016/j.cjca.2024.04.016

Collagen triple helix repeat-containing protein 1 is a novel biomarker of right ventricular involvement in pulmonary hypertension

Can J Cardiol. 2024 Apr 29:S0828-282X(24)00337-4. doi: 10.1016/j.cjca.2024.04.016. Online ahead of print.

Authors

Tetsuro Yokokawa¹, Kazuto Nishiura², Masataka Katahira², Yu Sato², Shunsuke Miura², Akihiko Sato², Takeshi Shimizu², Tomofumi Misaka³, Takamasa Sato², Takashi Kaneshiro², Masayoshi Oikawa², Akiomi Yoshihisa⁴, Koichi Sugimoto², Kenji Fukushima⁵, Kazuhiko Nakazato², Yasuchika Takeishi²

Affiliations

¹ Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan. Electronic address: yokotetu@fmu.ac.jp.
² Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.
³ Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan; Department of Community Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan.
⁴ Department of Cardiovascular Medicine, Fukushima Medical University, Fukushima, Japan; Department of Clinical Laboratory Sciences, Fukushima Medical University, Fukushima, Japan.
⁵ Department of Radiology and Nuclear Medicine, Fukushima Medical University, Fukushima, Japan.

PMID: 38692430
DOI: 10.1016/j.cjca.2024.04.016

Abstract

Background: Pulmonary hypertension leads to right ventricular failure, which is a major determinant of prognosis. Circulating biomarkers for right ventricular function are poorly explored in pulmonary hypertension. This study aimed to clarify the significance of collagen triple helix repeat-containing protein 1 (CTHRC1) as a biomarker of right ventricular failure in pulmonary hypertension.

Methods: A monocrotaline-induced pulmonary hypertension rat model was used to evaluate right ventricular CTHRC1 expression and its relationship with fibrosis. Next, human plasma CTHRC1 levels were measured in controls (n = 20), pulmonary arterial hypertension (n = 46), and chronic thromboembolic pulmonary hypertension (CTEPH) patients (n = 64) before the first and after the final balloon pulmonary angioplasty.

Results: CTHRC1 expression was higher in the right ventricles of rats with monocrotaline-induced pulmonary hypertension than in those of controls. CTHRC1 was co-localized with vimentin and associated with fibrosis in the right ventricles. Plasma CTHRC1 levels were higher in human pulmonary arterial hypertension (P = 0.006) and CTEPH patients (P = 0.011) than in controls. Plasma CTHRC levels were correlated with B-type natriuretic peptide (R = 0.355, P < 0.001), tricuspid lateral annular peak systolic velocity (R = -0.213, P = 0.029), and right ventricular fractional area change (R = -0.225, P = 0.017). Finally, plasma CTHRC1 levels were decreased after the final balloon pulmonary angioplasty (P < 0.001) in CTEPH.

Conclusions: CTHRC1 can be a circulating biomarker associated with right ventricular function and fibrosis in pulmonary hypertension and might reflect the therapeutic efficacy of balloon pulmonary angioplasty in CTEPH.

Keywords: Pulmonary hypertension; balloon pulmonary angioplasty; biomarker; chronic thromboembolic pulmonary hypertension (CTEPH); collagen triple helix repeat-containing protein 1 (CTHRC1).