Macrophage Migration Inhibitory Factor (MIF) is associated with higher collateralization grade in patients with coronary chronic total occlusions

Abstract

Purpose: Chronically total occluded coronary artery (CTO) is often associated with collateral circulation that is only partially supplying to the lack of antegrade blood flow. Therefore, variable degree of residual myocardial ischemia might still be present. The macrophage migration inhibitory factor (MIF), secreted by endothelial cells, has been showed to promote in vitro the recruitment of the endothelial progenitor cells to the ischemic tissues. It is still unknown whether MIF is involved in collateral formation of patients (pts) with CTO. We evaluated the possible correlation of MIF levels with the extent of collateral circulation in pts with CTO. Methods and results: Blood collection for MIF evaluation was performed in 32 consecutive patients (n=32) undergoing to percutaneous coronary intervention (PCI) of CTO at three different sites: a) Femoral arterial sheath (ART); 2) Tip of the guiding catheter proximal to CTO (PROX); 3) Tip of the microcatheter distal to CTO (DIST) after the occlusion was crossed, but not yet dilated. MIF was also assessed at ART and PROX level in 10 patients with normal coronary arteries, class ≤ 2 identified pts with Low Collateralization Grade (LCG; n=19), Rentrop class 3 identified pts with High Collateralization Grade (HCG; n=13). MIF was analyzed with a commercially available ELISA kit. Within CTO pts, a significant MIF increase was found across the 3 sampling sites (ART: 20.9±7.4 vs. PROX: 28.0±18.8 vs. DIST 39.4±20.6 ng/ml, p<0.01). MIF was significantly higher at DIST level in HCG as compared with LCG pts (45.2±23.9 vs. 35.5±17.6 ng/ml, p=0.05), while no difference was found at PROX (26.5±9.1 vs. 28.9±21.7 ng/ml, p=0.41) or ART level (18.7±5.2 vs. 22.3±8.4 ng/ml, p=0.42). Within CTRL pts, MIF was not significantly increased at the 2 sampling sites (ART: 18.7±7.4 vs. PROX: 15.6±5.3, p=0.10). Compared with CTRL pts, MIF was found significantly elevated in CTO pts at PROX (p=0.05), but not at ART (p<0.55) level. Conclusions: Higher MIF levels are found downstream to the arterial occlusion. This along with lower levels found proximal to the occlusion and at peripheral level suggest a loco-regional MIF production. In addition, the higher the MIF levels the higher the collateralization grade.