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. Issue 4 (21st April 2016)

• Record Type: Journal Article
• Authors: Müller, Karin A.L.; Rath, Dominik; Schmid, Martina; Schoenleber, Heiko; Gawaz, Meinrad; Geisler, Tobias; Müller, Iris I.
• Is Part Of: Clinical cardiology. Volume 39:Issue 4(2016)
• Page Start: 201
• Page End: 206
• Publication Date: 2016-04-21
• Subjects: Cardiology -- Periodicals; 616.12005
• DOI: 10.1002/clc.22509
• Languages: English
• ISSNs: 0160-9289

Abstract

Abstract: 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 < 0.001). Although the single plasma parameters showed an association with DM2 and CAD status, we could not confirm that the Gremlin‐1/MIF ratio is significantly different in patients stratified by DM2 and CAD ( P = 0.072). Hence, Gremlin‐1/MIF ratio was significantly lower in patients with ACS compared with SAP (1.1 ± 0.1 vs 4.4 ± 1.1; P = 0.003). 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.