Proteoglycan remodeling is accelerated in women with angina pectoris and diffuse myocardial fibrosis: the iPOWER Study

Background Women with angina and no obstructive coronary artery disease have an unfavourable prognosis, possibly due to coronary microvascular disease and diffuse myocardial fibrosis. In diffuse myocardial fibrosis myocardial extracellular matrix proteins, including the proteoglycans biglycan and versican are actively remodeled by matrix metalloproteinase. We investigated MMP-mediated degradation of biglycan and versican in women with possible DMF assessed by cardiac magnetic resonance T1 mapping. Methods Seventy-one women with angina pectoris and a coronary angiogram with no significant obstructive coronary artery disease (< 50% stenosis) were included. Asymptomatic age-matched women served as controls (n = 32). Matrix metalloproteinase 12 generated neo-epitope fragment of versican (VCANM) and MMP-9 generated fragment of biglycan (BGM) were measured in serum by specific competitive enzyme-linked immunosorbent assays (ELISAs). T1 mapping was performed by cardiac magnetic resonance with gadolinium (0.1 mmol/kg) using a look-locker pulse sequencing measuring T1 and extracellular volume. Results Both BGM and VCANM levels were higher in symptomatic women compared with controls; 31.4 ng/mL vs. 16.4 ng/mL (p < 0.001) and 2.1 ng/mL vs. 1.8 ng/mL (p < 0.001), respectively. Both BGM and VCANM were moderately correlated to global extracellular volume (r2 = 0.38, p < 0.001 and r2 = 0.26, p = 0.015 respectively). Conclusion Turnover of BGM and VCANM was increased in symptomatic women compared to asymptomatic women and associated to extracellular volume, supporting a link between angina with no obstructive coronary artery disease and fibrotic cardiac remodeling. The examined biomarkers may prove to be suitable for monitoring active extracellular matrix remodeling.