Full Papers
Fibroblast activities are associated with prolonged QTc and pulmonary arterial hypertension in patients with systemic sclerosis
C.T.H. Nielsen1, S. Holm Nielsen2, S. Søndergaard Korsholm3, A.C.P. Diederichsen4, J. Bonde5, M.A. Karsdal6, A.-C. Bay-Jensen7, L.P. Diederichsen8
- Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, Denmark. christoffer.tandrup.nielsen.01@regionh.dk
- Immunoscience, Nordic Bioscience, Herlev, Denmark.
- Department of Rheumatology, Odense University Hospital, Odense, Denmark.
- Department of Cardiology, Odense University Hospital, Odense, Denmark.
- Department of Rheumatology, Odense University Hospital, Odense, Denmark.
- Immunoscience, Nordic Bioscience, Herlev, Denmark.
- Immunoscience, Nordic Bioscience, Herlev, Denmark.
- Center for Rheumatology and Spine Diseases, Copenhagen University Hospital, Rigshospitalet, Copenhagen, and Department of Rheumatology, Odense University Hospital, Odense, Denmark.
CER18057
Full Papers
PMID: 40095647 [PubMed]
Received: 08/08/2024
Accepted : 05/02/2025
In Press: 12/03/2025
Abstract
OBJECTIVES:
In systemic sclerosis patients (SSc), we aimed at exploring the potential of serum biomarkers of fibrosis and immune-cell activity to detect subclinical heart involvement determined by electrocardiographic (ECG) alterations.
METHODS:
A panel of extracellular matrix (ECM) turnover biomarkers quantifying type III and VI collagen formation (PRO-C3 and PRO-C6), type IV collagen turnover (PRO-C4), MMP-degraded type III, IV, VI and VII collagen (C3M, C4M, C6M and C7M), human neutrophil elastase degraded elastin and calprotectin (ELA-HNE and CPa9-HNE), MMP-degraded C-reactive protein (CRPM), MMP-degraded and citrullinated vimentin (VICM) were measured by competitive ELISAs in serum from 102 well-characterised systemic sclerosis patients. Correlations to ECG-changes as well as clinical and paraclinical manifestations were explored.
RESULTS:
PRO-C3 and PRO-C6, biomarkers of fibroblast activation, were significantly increased in patients with prolonged QTc (>450ms) (p=0.043 and p=0.027, respectively), while no difference was detected for PRO-C4, C3M, C4M, C6M, and C7M. The ELA-HNE biomarker was significantly reduced in patients with prolonged QTc (>450ms). No difference was found for the CPa9-HNE, CRPM, VICM, and C4G. The PRO-C3 and PRO-C6 biomarkers were also significantly increased in the patients with pulmonal arterial hypertension (PAH) (p=0.041 and p=0.019, respectively), and increased with NYHA class (p=0.024 and p=0.045, respectively). In addition, C6M were significantly increased with NYHA class (p=0.021).
CONCLUSIONS:
Patients with SSc and prolonged QTc, presence of PAH and high NYHA class presented an altered tissue turnover, particularly associated with increased fibroblast activation. Our study indicates that serum-based biomarkers could serve as convenient biomarkers of subtle cardiac disease in SSc but further studies are needed to confirm this.
