A fragment of C-terminal type VIa3 collagen (endotrophin)
Fibrosis is a hallmark feature of HFpEF pathology, acting as a driver of outcome. Understanding the intricate pathways that lead to fibrogenesis, and how they ultimately impact pathogenesis, is important for understanding how to treat HFpEF. We have developed a biomarker of fibroblast activity, PRO-C6, which independently and with high precision can identify a subset of HFpEF patients with a very elevated risk of adverse outcome.
Endotrophin is a signaling molecule released from collagen type VI (COL VI). Endotrophin can be measured by the PRO-C6 assay, which quantifies the levels of COL VI formation.
PRO-C6 and C3M in serum (sPRO-C6, sC3M) and urine (uPRO-C6, uC3M) were measured by ELISA in 663 patients with T1D ranging from normoalbuminuric to macroalbuminuric. Association of the biomarkers with mortality, CVEs, heart failure, decline in estimated glomerular filtration rate (eGFR) ≥30%, and end-stage renal disease (ESRD) were tested in Cox proportional hazards models after log2 transformation and adjusted for relevant clinical characteristics. Hazard ratios (HRs) were reported per doubling of biomarker levels. High levels of sPRO-C6 were independently associated with a higher risk of all-cause mortality (HR 2.26 [95% CI 1.31-3.87], P \u003c 0.0031). There was an association with higher risk of CVEs (n = 94) and heart failure (n = 28) but not after adjustment (P ≥ 0.58). In relation to renal outcomes, adjusted sPRO-C6 was associated with a higher risk of eGFR decline ≥30% in T1D, with eGFR \u003e45 and \u003e30 mL/min/1.73 m2, and with a higher risk of ESRD (all P ≤ 0.03). Higher uPRO-C6 was associated with a lower risk of decline in eGFR.
We examined a cohort of 49 IgAN and 47 AAV patients. A validation cohort of 85 IgAN patients was included. Endotrophin (ETP) was measured in serum (S-ETP) and urine (U-ETP/Cr) samples, taken on the same day before renal biopsy was performed, using the ELISA PRO-C6. The biopsies were evaluated for interstitial fibrosis and tubular atrophy according to the Banff and MEST-C scores. S-ETP and U-ETP/Cr levels correlated with kidney function, increased with CKD severity, correlated with the extent of interstitial fibrosis and gradually increased with increasing degree of interstitial fibrosis and tubular atrophy. ETP outperformed the known fibrosis biomarker Dickkopf-3 for discrimination of patients with high fibrotic burden. The association of S-ETP and U-ETP/Cr with the level of kidney fibrosis was confirmed in the validation cohort.
Lung Fibrosis, COPD, HepNIT Panel™: Hepatic Non-invasive Tests, Bridging Fibrosis, Tissue Fibrosis, Fibrosis / Fibroblasts, Kidney Disease Activity, Kidney Outcome, Kidney Preclinical, Heart Fibrosis, Atherosclerotic Plaque Instability, Heart Outcome, Tissue Fibrosis, Mucosal Damage Resolution, Systemic Sclerosis
Pro-fibrotic signaling, ECM formation
PROC6, nordicPRO-C6™, Endotrophin
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