High Plasma Levels of Gremlin‐1 and Macrophage Migration Inhibitory Factor, but Not Their Ratio, Indicate an Increased Risk for Acute Coronary Syndrome in Patients With Type 2 Diabetes Mellitus

摘要

Background Chronic inflammation promotes atherosclerosis and is a prognostic factor in coronary artery disease (CAD). Patients with type 2 diabetes mellitus (DM2) are at risk for progressive atherosclerosis. Macrophage migration inhibitory factor (MIF) is a key player in atherosclerosis, mediating pro-inflammatory responses. Its endogenous antagonist Gremlin-1 inhibits foam-cell formation and atheroprogression by binding MIF, neutralizing its proatherosclerotic functions. Hypothesis Plasma levels of MIF and Gremlin-1 correlate with the stability of CAD in patients with DM2. Method We assessed plasma levels of Gremlin-1 and MIF in 198 nondiabetic and 88 diabetic patients with symptomatic CAD using enzyme-linked immunosorbent assays. Results Plasma levels of Gremlin-1 were higher DM2 patients (278.8 ± 16.6 vs 224.7 ± 6.7 ng/mL; P = 0.001). MIF levels were elevated but not significantly increased in DM2 ( P = 0.098). Interestingly, we found that Gremlin-1 plasma levels were significantly higher in diabetic patients with stable angina pectoris (SAP; n = 53) or acute coronary syndrome (ACS; n = 35) compared with nondiabetic patients with SAP ( P = 0.008 and P = 0.011, respectively). MIF levels were significantly higher in diabetic patients with ACS compared with SAP ( P Conclusions Diabetic patients with ACS show increased levels of Gremlin-1 and MIF, leading to unfavorable Gremlin-1/MIF ratios. However, DM2 alone is not associated with low Gremlin-1/MIF ratios.