Impact of counterbalance between macrophage migration inhibitory factor and its inhibitor Gremlin-1 in patients with coronary artery disease

2014 ◽  
Vol 237 (2) ◽  
pp. 426-432 ◽  
Author(s):  
Iris I. Müller ◽  
Karin A.L. Müller ◽  
Athanasios Karathanos ◽  
Heiko Schönleber ◽  
Dominik Rath ◽  
...  
2020 ◽  
Vol 24 (3) ◽  
pp. 376-385
Author(s):  
Feyan Abdullah ◽  
Ruqaya Al-Barzinj

Background and objective: Coronary artery disease is a chronic inflammatory disease in which many risk factors and inflammatory mediators, including macrophage migration inhibitory factor, are involved. This study aimed to estimate macrophage migration inhibitory factor level in coronary artery disease patients in regard to age, gender, and smoking. Methods: A total of 138 coronary artery disease patients and 38 coronary artery disease free control subjects were admitted to surgical specialty hospital-cardiac center in Erbil city, Iraq between January and December 2017. Plasma macrophage migration inhibitory factor concentration was measured by enzyme linked immunosorbent assay. Results: Patients and controls were categorized into subgroups according to age (<55 and ≥55 years), gender (women and men), and smoking status (smokers and non-smokers). Macrophage migration inhibitory factor level in every coronary artery disease subgroup (age, gender, and smokers) patients increased significantly compared to the same control subgroups (P <0.05). Macrophage migration inhibitory factor level showed a higher level in coronary artery disease patients subgroups (≥55 years, female, smokers) compared to their corresponding coronary artery disease subgroups (<55 years, male, and non smokers). Macrophage migration inhibitory factor demonstrated a significant positive correlation with fibrinogen and high sensitivity C-reactive protein, insignificant positive correlation with age, total cholesterol, low density lipoprotein, and insignificant negative correlation with high density lipoprotein-cholesterol (P >0.05). Conclusion: This study demonstrated the diagnostic value of macrophage migration inhibitory factor elevation in coronary artery disease patients if compared with coronary artery disease free subjects, meanwhile suggesting that age, gender, and smoking had no direct role in macrophage migration inhibitory factor elevation considering their secondary minor contributions in macrophage migration inhibitory factor circulation. Keywords: Coronary; Macrophage; Age; Gender; Smoking.


2014 ◽  
Vol 176 (3) ◽  
pp. 923-929 ◽  
Author(s):  
Iris I. Müller ◽  
Madhumita Chatterjee ◽  
Martina Schneider ◽  
Oliver Borst ◽  
Peter Seizer ◽  
...  

2016 ◽  
Vol 38 (2) ◽  
pp. 801-808 ◽  
Author(s):  
Sandra Beck ◽  
Thomas Simmet ◽  
Iris Müller ◽  
Florian Lang ◽  
Meinrad Gawaz

Background/Aims: The counterbalance of macrophage migration inhibitory factor (MIF) and Gremlin-1 is a useful tool to predict the acuity of coronary artery disease (CAD) and plaque stability. Gremlin1 is an endogenous antagonist of MIF and therefore influences plaque vulnerability. This study was designed to elucidate the mechanistic basis determining the biophysical binding of Gremlin-1 to MIF. Methods: An in silico model suggested that several charged C-terminal amino acids are crucial in mediating Gremlin-1/MIF-binding. We produced several single amino acid exchange mutants of Gremlin-1 by site-directed mutagenesis. These Gremlin-1 mutants were tested for their ability to reduce MIF effects on monocytes. Results: We observed that the critical element of the Gremlin-1 molecule for regulating MIF-induced chemotactic activity lies at the C-terminal region. A single amino acid exchange of an arginine to an alanine residue is sufficient to abolish the antagonistic effect of Gremlin-1 on MIF. Therefore, the Gremlin-1 mutant R172A failed to reduce MIF-induced monocyte differentiation into macrophages. Conclusion: Gremlin-1 C-terminus is essential for antagonizing MIF effects. Our results could offer a novel strategy utilizing Gremlin-1 to target pro-inflammatory effects of MIF in various diseases.


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