Temporal association between circulating proteolytic, inflammatory and neurohormonal markers in patients with coronary ectasia

The prevalence of coronary ectasia (CE) appears to rise in recent years. However, the pathogenetic mechanisms that underlie this entity are not understood. We hypothesized that dysregulation of circulating matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinase (TIMPs) contributes to ectasia formation. We also evaluated the association of MMP with inflammatory or the neurohormonal markers. Methods: We screened coronary angiographic procedures conducted in our hospital. Thirty-four patients with CEs were identified; 17 with a single ectasia and 17 with generalized ectasias. Two control groups; patients with atherosclerotic coronary disease (n = 26) and patients with normal coronary arteries (n = 27) were chosen randomly. Serum levels of MMP-2, MMP-3 and TIMP-1 were determined by ELISA. Pro B-type natriuretic peptide (proBNP) and high sensitivity C-reactive protein (hsCRP) serum levels were also measured. Results: Serum levels of MMP-2, MMP-3, TIMP-1, proBNP and hsCRP did not differ between the three groups of patients. However, subgroup analysis demonstrated that MMP-3 level is significantly lower in patients with generalized CEs compared to those with single vessel ectasia. We also found a statistically significant correlation between proBNP and MMP-2/TIMP-1 (for MMP-2: r2 = 0.3, p = 0.003 and for TIMP-1 r2 = 0.42, p < 0.000l). By performing subgroup analysis we found that this correlation is only demonstrated in patients with CEs. No correlation was demonstrated between hsCRP and MMPs/TIMP. Conclusions: These observations suggest that MMP/TIMP imbalance is present in patients with generalized CE and may contribute to ectasia formation. This imbalance could be mediated by BNP.