Effect of a Peptide Construct on Differentiated Macrophage MMP-2 and MMP-9 Levels of Varicose Patients

Abstract

Background: The Matrix Metalloproteinase (MMPs) secreted from macrophages can affect the extracellular matrix remodeling process and improve varicose veins. Aim: The aim of this study was to investigate the MMP-2 and MMP-9 gene expression and activity levels in the differentiated macrophages M2 of subjects with varicose veins, and to evaluate a peptide construct on their catalytic functions. Methods: The macrophages were differentiated from the monocytes using M-CSF. The MMP-2 and MMP-9 gene expression and activity levels were measured by RT-qPCR and Zymography techniques, respectively. A peptide construct (ESLCG) was predicted with bioinformatics tools, and was prepared for the study of enzyme functions as compared to Batimastat. Furthermore, the docking studies were obtained for the evaluation of interactions between peptide construct, Batimastat and enzyme 3D structures. Results: The results showed significant increases in MMP2 and MMP9 gene expression levels (P <0.001 and P <0.004, respectively) and gelatinolytic activities (P <0.001 and P <0.0001, respectively) in the macrophages. In agreement with the inhibitory effects of Batimastat, the peptide construct inhibited the MMP-2 and MMP-9 gelatinolytic activities up to 6.8 and 6.5 folds in the concentration of 150 µM. The docking analyses showed that the Lys187, Arg98, Leu49, Gly189, Leu190, Met97, Tyr53 and Phe57 residues of MMP-2 and the Leu187, His190, Glu402, His401, His405 and His411 residues of MMP-9 are interacted with the atoms of Batimastat and ESLCG peptide. Conclusion: The ESLCG peptide may be applied as an inhibitor of MMP-2 and MMP-9 enzymes in the subjects with varicose veins.

Correlation analysis between TSP2, MMP-9 and perihematoma edema, as well as the short-term prognosis of patients with hypertensive intracerebral hemorrhage

“…Once the body has tumor, inflammation, and other pathological conditions, the level of MMP-9 is significantly increased. It has been shown that the expression of MMP-9 in the brain tissue of patients with cerebral hemorrhage is up-regulated; hydrolyzed laminin, collagen fibers, and other causes of cell tight junctions and extracellular matrix molecules are destroyed, the permeability of cerebral vascular barrier is increased, and the occurrence of cerebral edema is promoted (10,11). Mouchtouris et al (12) found that the MMP-9 levels of hypertensive cerebral hemorrhage patients with neurological symptoms within 24 hours were significantly increased, and were positively correlated to the degree of edema around the hematoma as well as to patients with consciousness disturbance.…”