Circulating multimarker profile of patients with symptomatic heart failure supports enhanced fibrotic degradation and decreased angiogenesis

Background: Heart failure (HF) involves myocardial fibrosis and dysregulated angiogenesis. Objective: We explored whether biomarkers of fibrosis and angiogenesis correlate with HF severity. Methods: Biomarkers of fibrosis [procollagen types I and III (PIP and P3NP), carboxyterminal-telopeptide of type I collagen (ICTP), matrix metalloproteases (MMP2 and MMP9), tissue inhibitor of MMP1 (TIMP1)]; and angiogenesis [placental growth factor (PGF), vascular endothelial growth factor (VEGF), soluble Fms-like tyrosine kinase-1 (sFlt1)] were measured in 52 HF patients and 19 controls. Results: P3NP, ICTP, MMP2, TIMP1, PGF, and sFlt1 levels were elevated in HF, while PIP/ICTP, PGF/sFlt1, and VEGF/sFlt1 ratios were reduced. PIP/ICTP, MMP-9/TIMP1, and VEGF/sFlt1 ratios were lowest among patients with severe HF. Conclusions: Severe HF is associated with collagen breakdown and reduced angiogenesis. A multimarker approach may guide therapeutic targeting of fibrosis and angiogenesis in HF.