Title:Effect of a Peptide Construct on Differentiated Macrophage MMP-2 and MMP-9 Levels of Varicose Patients
Volume: 25
Issue: 40
Author(s): Golnaz Esfandiari, Azim S. Biranvand, Adeleh Poursaleh, Naser Kakavandi, Fahimeh Fattahi, Ghasem Ghasempour, Elham Bahraini, Mohsen Khosravi and Mohammad Najafi*
Affiliation:
- Biochemistry Department, Faculty of Medical Sciences, Iran University of Medical Sciences, Tehran,Iran
Keywords:
MMP-2, MMP-9, varicose, macrophage, peptide construct, monocytes.
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.