Colchicine modulates TIMP1, MMP1, and pMAP4 expression to enhance extracellular matrix degradation in 3T3 fibroblast-mediated myocardial infarction; [Colchicina modula la expresión de TIMP1, MMP1 y pMAP4 para potenciar la degradación de la matriz extracelular en el infarto de miocardio mediado por fibroblastos 3T3]

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Saskia Dyah Handari, Mohammad Saifur Rahman, Djanggan Sargowo, Aulanni Aulanni, Bayu Lestari, Delvac Oceandy

2024 Journal of Pharmacy and Pharmacognosy Research Vol. 12 Issue 3 Article Cited by 1 Quartile

Abstract

Context: Cardiovascular disease is a leading cause of mortality worldwide. Following acute myocardial infarction (AMI), cardiac cells release many cytokines and proteolytic enzymes that regulate the extracellular matrix (ECM), including matrix metalloproteinases (MMPs), tissue inhibitor of metalloproteinases (TIMPs), and phosphorylated microtubule-associated protein 4 (Phospho/pMAP4). Aims: To analyze the role of colchicine in ECM regulation post-ischemic in cell line culture towards MMPs, TIMPs, and pMAP4. Methods: This in vitro experimental study was conducted on the 3T3 fibroblast cell line subjected to hypoxic conditions (CoCl2 treatment) and compared with 3T3 cells experiencing hypoxia/ischemic and colchicine treatment. MMP-1, TIMP-1, and pMAP4 expression were measured using flow cytometry. Data analysis was performed using One-Way ANOVA with a 95% confidence level. Results: Treatment with colchicine in the 3T3 fibroblast cell culture regulated the extracellular matrix by increasing TIMP-1 expression and reducing MMP-1 and pMAP4 expression (p<0.0001) following ischemic conditions induced by CoCl2. Conclusions: Colchicine effectively mitigates ECM degradation by enhancing TIMP-1 expression and inhibiting MMP-1 activity and pMAP4 expression post-ischemic conditions. © 2024 Academic Association of Pharmaceutical Sciences from Antofagasta (ASOCIFA). All rights reserved.

Affiliations

Doctoral Program of Medical Science, Brawijaya University, East Java, Malang, Indonesia; Medical Faculty, Ciputra University, Surabaya, Indonesia; Department of Cardiology and Cardiovascular Medicine, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, Indonesia; Department of Cardiology and Vascular Medicine, Faculty of Medicine, Universitas Brawijaya, East Java, Malang, Indonesia; Department of Chemistry, Faculty of Sciences, Universitas Brawijaya, Malang, Indonesia; Division of Cardiovascular Sciences, University of Manchester, United Kingdom