Extracellular matrix collagen biomarkers levels in patients with chronic thromboembolic pulmonary hypertension
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Extracellular matrix collagen biomarkers levels in patients with chronic thromboembolic pulmonary hypertension Wenyi Pang1,2,3 · Zhu Zhang1,2,3 · Yunxia Zhang1,2 · Meng Zhang1,2 · Ran Miao4,5 · Yuanhua Yang4,5 · Wanmu Xie1,2,5 · Jun Wan1,2,5 · Zhenguo Zhai1,2,3,5 · Chen Wang1,2,3,5 Accepted: 30 October 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Limited data exist on changes in the extracellular matrix (ECM) collagen biomarkers levels during chronic thromboembolic pulmonary hypertension (CTEPH) development. This study aimed to investigate ECM collagen biomarkers levels in stable patients with CTEPH. Patients with CTEPH and healthy persons were enrolled. Serum levels of procollagen III N-terminal peptide (PIIINP), carboxyterminal propeptide of type I procollagen (PICP), matrix metalloproteinases (MMP2), MMP9, and tissue inhibitor of metalloproteinases 1(TIMP1) were measured by ELISA. Clinical data coincident with samples were collected. The pulmonary endarterectomy (PEA) and control pulmonary artery tissue samples were analyzed for genetic and immunohistochemical differences. The serum concentrations of PIIINP, PICP, MMP2, and MMP9 decreased significantly in CTEPH patients compared to healthy controls (P < 0.001 for each). CTEPH patients had higher serum concentrations of TIMP1 (median, 111.97 [interquartile range, 84.35–139.93]) compared to healthy controls (74.97 [44.03–108.45] ng/mL, P < 0.001). The MMP2 to TIMP1 ratio was lower in patients than in the controls (P < 0.001). After adjusting for the body mass index (BMI), the MMP2 to TIMP1 ratio correlated negatively with pulmonary vascular resistance (PVR) (r = − 0.327, P = 0.025). Increased TIMP1 (P = 0.04) gene expression was identified in tissues of CTEPH patients. Immunohistochemistry results of vascular walls substantiated qRT-PCR results. This study indicates that ECM collagen biomarkers levels were significantly different in stable patients with CTEPH and healthy controls with significantly increased TIMP1 and decreased MMP2 and MMP9. Differences in TIMP1 expression should be expected not only among healthy controls and patients serum, but also across pathological tissue regions. These findings suggest that the state of vascular remodeling in pulmonary vascular bed in stable patients may be represented by ECM collagen biomarkers levels. We conclude that TIMP1 may play an important role in pulmonary vascular reconstruction in stable CTEPH patients. Keywords Chronic thromboembolic pulmonary hypertension · Matrix metalloproteinases · Tissue inhibitor of metalloproteinases · Extracellular matrix
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s11239-020-02329-8) contains supplementary material, which is available to authorized users. * Zhenguo Zhai [email protected] 1
Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, No 2, East Yinghua Road, Chaoyang District, Beijing, People’s Republic of Chi
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