Macrophage Migration Inhibitory Factor Is Enhanced in Acute Coronary Syndromes and Is Associated with the Inflammatory Response

Abstract

BackgroundChronic inflammation promotes atherosclerosis in cardiovascular disease and is a major prognostic factor for patients undergoing percutaneous coronary intervention (PCI). Macrophage migration inhibitory factor (MIF) is involved in the progress of atherosclerosis and plaque destabilization and plays a pivotal role in the development of acute coronary syndromes (ACS). Little is known to date about the clinical impact of MIF in patients with symptomatic coronary artery disease (CAD).Methods and ResultsIn a pilot study, 286 patients with symptomatic CAD (n = 119 ACS, n = 167 stable CAD) undergoing PCI were consecutively evaluated. 25 healthy volunteers served as control. Expression of MIF was consecutively measured in patients at the time of PCI. Baseline levels of interleukin 6 (IL-6), “regulated upon activation, normal T-cell expressed, and secreted” (RANTES) and monocyte chemoattractant protein-1 (MCP-1) were measured by Bio-Plex Cytokine assay. C-reactive protein (CRP) was determined by Immunoassay. Patients with ACS showed higher plasma levels of MIF compared to patients with stable CAD and control subjects (median 2.85 ng/mL, interquartile range (IQR) 3.52 versus median 1.22 ng/mL, IQR 2.99, versus median 0.1, IQR 0.09, p<0.001). Increased MIF levels were associated with CRP and IL-6 levels and correlated with troponin I (TnI) release (spearman rank coefficient: 0.31, p<0.001). Patients with ACS due to plaque rupture showed significantly higher plasma levels of MIF than patients with flow limiting stenotic lesions (p = 0.002).ConclusionTo our knowledge this is the first study, demonstrating enhanced expression of MIF in ACS. It is associated with established inflammatory markers, correlates with the extent of cardiac necrosis marker release after PCI and is significantly increased in ACS patients with “culprit” lesions. Further attempts should be undertaken to characterize the role of MIF for risk assessment in the setting of ACS.

Macrophage Migration Inhibitory Factor Limits Activation-Induced Apoptosis of Platelets via CXCR7-Dependent Akt Signaling

“…Previously, we reported elevated plasma levels of MIF in patients with acute coronary syndrome as compared with symptomatic coronary artery disease and healthy subjects, which was associated with other systemic inflammatory markers like C-reactive protein and IL-6 and correlated with troponin release. 16 Platelets having been acknowledged as a substantial source of MIF, these clinical observations need to be reevaluated to determine the contribution of platelet-derived MIF in these contexts. Nevertheless, MIF coming from a paracrine source at the site of vascular inflammation, injury, atherosclerotic lesions, or other circulating cells like monocytes and macrophages is enough to register the changes as deciphered here even in the absence of plateletderived MIF.…”

“…Patients with acute coronary syndrome caused by plaque rupture show significantly higher plasma levels of MIF than patients with flow-limiting stenotic lesions. 16 Platelets have been characterized as a source of MIF, which when released on platelet activation can induce migration of monocytes along with SDF-1α/CXCL12. 17 However, the potential effect of MIF on platelets themselves remained elusive.…”

Platelets, inflammation and anti-inflammatory effects of antiplatelet drugs in ACS and CAD

“…Platelets harbour three femtogram MIF/cell and -owing to their abundance in circulation -might have a profound influence in modulating vascular inflammation by instigating monocyte migration (34) or potentially contributing to elevated plasma MIF levels in patients with acute myocardial infarction (MI) (35). MIF rescues platelets from undergoing apoptosis through CXCR7 like SDF-1α and CXCL11 and sustains platelet life span in circulation as well (32).…”

MBL2 and MIF gene polymorphisms in cardiovascular patients with atherosclerotic lesions undergoing heart valve replacement

“…Fragile plaques are characterized by high inflammatory activity coupled with high contents of inflammatory cells such as monocyte/macrophage and chemokines playing an important role in plaque rupture [27].…”