Journal Article

Inhibition of C-reactive protein induced expression of matrix metalloproteinases by atorvastatin in THP-1 cells

Mahajan, Nitin, Dhawan, Veena

2010

Overview

The role of CRP as a mediator in atherosclerosis and inflammation is being investigated worldwide. In the present study, the effect of CRP on matrix metalloproteinases (MMP)-1, 2, 9, and their tissue inhibitor (TIMP-1) gene expression in THP-1 monocytic cell line was investigated. Specific mitogen activated protein (MAP) kinase (ERK, p38, and JNK) inhibitors were used to elucidate the signaling pathways involved. Effect of atorvastatin was determined in the presence of CRP on the expression of genes. Time and dose-dependent experiments were performed in the presence of CRP. The results showed that the treatment of THP-1 cells with 100 μg of CRP/ml/10⁶ cells for 24 h enhanced the expression of MMPs and TIMP-1 genes significantly. CRP upregulated the expression of these genes via FcγRII and utilized ERK signaling pathway to transduce signals. Atorvastatin was able to significantly attenuate CRP-induced MMPs expression and augmented TIMP-1 gene expression significantly. In conclusion, CRP is not only a risk marker for vascular events, but also directly involved in the mechanisms leading to remodeling and destabilization of atherosclerotic plaque. Also, atorvastatin serves as potential therapeutic modality to curb these harmful events.

• Publisher: Boston : Springer US,Springer US,Springer,Springer Nature B.V
• Subject: Anticholesteremic Agents - pharmacology / Antilipemic agents / Atherosclerosis / Atorvastatin Calcium / Biochemistry / Biomedical and Life Sciences / C-reactive protein / C-Reactive Protein - antagonists & inhibitors / C-Reactive Protein - pharmacology / Cardiology / Cell Line / Cellular biology / Dose-Response Relationship, Drug / Gene expression / Gene Expression Regulation, Enzymologic - drug effects / Genes / Heptanoic Acids - pharmacology / Humans / Inflammation / Life Sciences / MAP Kinase Signaling System - drug effects / MAP Kinase Signaling System - physiology / Matrix Metalloproteinase 1 - genetics / Matrix Metalloproteinase 1 - metabolism / Matrix Metalloproteinase 2 - genetics / Matrix Metalloproteinase 2 - metabolism / Matrix Metalloproteinase 9 - genetics / Matrix Metalloproteinase 9 - metabolism / Medical Biochemistry / Mitogen-Activated Protein Kinases - antagonists & inhibitors / Mitogen-Activated Protein Kinases - genetics / Mitogen-Activated Protein Kinases - metabolism / Monocytes - cytology / Monocytes - drug effects / Monocytes - physiology / Oncology / Proteases / Proteins / Pyrroles - pharmacology / Receptors, IgG - metabolism / Signal transduction / Statins / Tissue Inhibitor of Metalloproteinase-1 - genetics / Tissue Inhibitor of Metalloproteinase-1 - metabolism / Toy industry