Plasma Macrophage Migration Inhibitor Factor Is Elevated in Response to Myocardial Ischemia

Abstract

BackgroundMacrophage migration inhibitory factor (MIF) is a key regulator of inflammatory responses, including in the heart. Plasma MIF is elevated early in the course of acute myocardial infarction. In this study, we hypothesized that plasma MIF may also be increased in acute myocardial ischemia.Methods and ResultsPatients undergoing cardiac stress test (stress nuclear myocardial perfusion scan or stress echocardiography) were recruited. Twenty‐two patients had a stress test indicative of myocardial ischemia and were compared with 62 patients who had a negative stress test. Plasma MIF was measured by ELISA before and after the stress test. MIF was also measured in patients with peripheral arterial occlusive disease before and after exercise causing claudication. Gene and protein expression of MIF was measured in mouse cardiac and skeletal muscle tissue by real‐time polymerase chain reaction and western blot, respectively. Plasma MIF was elevated at 5 and 15 minutes after stress (relative to before stress) in patients with a positive test, compared with those with a negative test. In contrast, high‐sensitivity troponin T and C‐reactive protein were not altered after stress in either group. MIF was not altered after exercise in PAOD patients, despite the occurrence of claudication, suggesting that plasma MIF is not a marker for skeletal muscle ischemia. This may be explained by a lower gene and protein expression of MIF in skeletal muscle than the heart.ConclusionsOur results suggest that plasma MIF is an early marker for acute myocardial ischemia.

A comparison of macrophage migration inhibitory factor with C reactive protein in diabetic hypertensive patients with myocardial infarction that underwent primary percutaneous coronary intervention

“…According to the findings of this study, the levels of MIF, and hs-CRP increased sig-nificantly in all MI patients compared to the control group, with this finding being in agreement with past research (11)(12)(13). Although the MIF is formed by numerous cell types in the human atherosclerotic plaque (14), myocardium is the main source of circulating MIF because of its high MIF content (15). Unlike many cytokines, MIF could be released rapidly with no need for de novo synthesis due to the constitutive expression of MIF and its storage in intracellular pools (16).…”

Correlation between Plasma Macrophage Migration Inhibitory Factor Levels and Long-Term Prognosis in Patients with Acute Myocardial Infarction Complicated with Diabetes

“…Animal experiments demonstrated that the main source of MIF in the early phase after myocardial infarction is necrotic cardiomyocytes and its secretion pattern is characterized by direct, massive, and rapid release under ischemic stimulation, which is not dependent on de novo synthesis [ 10 , 18 ]. Fan et al [ 19 ] found that the MIF gene expression levels in cardiomyocytes were 30 times higher than that in skeletal muscle cells. Chan et al [ 3 ] established a mouse coronary occlusion model and found that the MIF content in the damaged myocardium decreased by approximately 40%, and a loss of MIF in the damaged cardiomyocyte was also detected.…”

MIF family cytokines in cardiovascular diseases and prospects for precision-based therapeutics

“…White et al explored the role of MIF in mediating inflammatory responses following acute myocardial ischemia and found MIF to be rapidly released from the damaged myocardium into the circulation [88]. Plasma MIF levels also have been reported to be associated with infarct size and the extent of post-infarct cardiac remodeling [89]. Mice with genetic Mif -deficiency were found to be protected from prolonged and severe ischemia reperfusion injury, and this effect was associated with reduced expression of inflammatory cytokines, a decrease in the myocardial infiltration of neutrophils and macrophages, and increased macrophage apoptosis [90].…”