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

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.

Screening and Risk Assessment of Coronary Artery Disease in Patients With Type 2 Diabetes: An Updated Review

“…Hao's et al study has indicated that diabetic patients with CAD have higher levels of serum vaspin compared to diabetics without CAD and healthy individuals (27). in vivo 33: 1039-1049 (2019) Müller et al, have examined whether blood Gremlin-1 and macrophage migration inhibitory factor (MIF) might be related to CAD and the risk of acute coronary syndrome (ACS) ( Table I) (31). MIF is a pro-inflammatory factor which regulates monocyte recruitment, leading to atheroprogression and plaque instability (32).…”

Circulating microRNA-92a level predicts acute coronary syndrome in diabetic patients with coronary heart disease

“…Patients with coronary heart disease (CHD) and T2DM, as compared with nondiabetic patients, often have complicated vascular lesions of increasing severity as well as multivessel and diffuse vasculopathy [3]. Previous studies point to several circulating biomarkers related to the incidence of ACS in T2DM patients, such as glycosylated hemoglobin (HbA1c) [4], B-type natriuretic peptide (BNP) [5], phospholipid protein [6], gremlin 1, and macrophage migration inhibitory factor [7]. However, these biomarkers are of limited use because they are nonspecific.…”

Risk factors of heart disease in nurses

“…[ 23 ] The suitability of blood sugar levels, controlling of atherosclerosis progression and inflammatory factors effective in this area, and improvement of platelet function reduced the incidence of acute coronary syndromes. [ 29 30 ]…”