Assessment of plasma level of matrix metalloproteinase-9 in patients with sickle cell disease and its relationship to myocardial iron overload

Abstract

Background Cardiac iron overload is secondary to chronic blood transfusion in patients with sickle cell disease (SCD). Iron overload cardiomyopathy is a restrictive cardiomyopathy associated with systolic and diastolic dysfunction. Matrix metalloproteinases (MMPs) are a family of zinc-dependent endopeptidases responsible for tissue remodeling. Many studies offer strong evidence for the role of MMP-9 in left ventricular (LV) remodeling. Objective The authors aimed to detect the plasma levels of MMP-9 in patients with SCD and its relationship to myocardial iron overload. Materials and methods A case–control study was carried out on 75 patients with SCD and 75 age-matched and sex-matched healthy controls. Assessment of cardiac iron overload in patients by MRI T2* was performed. Plasma MMP-9 levels were measured for patients and controls using enzyme-linked immunosorbent assay. Results Patients with SCD had significantly higher levels of MMP-9 than controls. There was a highly significant relationship between plasma levels of MMP-9 and each of cardiac T2* and serum ferritin. Patients with vaso-occlusive crises (VOC) greater than 5/year had significantly higher levels of MMP-9 than those with VOC less than or equal to 5 /year. Conclusion MMP-9 seems to be a useful marker in patients with SCD. Patients with cardiac T2* less than 20 ms, serum ferritin greater than 1000 ng/ml, and recurrent VOC greater than 5/year had significantly higher MMP-9 serum levels than others.

Acetylated oligopeptide and N‐acetylcysteine protect against iron overload‐induced dentate gyrus hippocampal degeneration through upregulation of Nestin and Nrf2/HO‐1 and downregulation of MMP‐9/TIMP‐1 and GFAP

“…Specifically, MMP‐9 is released by numerous brain cells, including hippocampal neurons, endothelial cells, and astrocytes 12 . There is evidence for free radicals and oxidative stress involvement in triggering MMP‐9 activation 13 . Tissue inhibitor metalloproteinase‐1 (TIMP‐1) is an inhibitor of MMP‐9 activity.…”

“…12 There is evidence for free radicals and oxidative stress involvement in triggering MMP-9 activation. 13 Tissue inhibitor metalloproteinase-1 (TIMP-1) is an inhibitor of MMP-9 activity. Normally, the dynamic equilibrium between MMPs and TIMPs is maintained.…”