Targeting the CCL2-CCR2 signaling pathway: potential implications of statins beyond cardiovascular diseases.

BACKGROUND: The chemokine ligand CCL2 and its cognate receptor CCR2 have been implicated in the pathogenesis of a wide variety of diseases. Hence, the inhibition of the CCL2/CCR2 signaling pathway has been of great attention in recent studies. Among suggested medications, statins known as HMG-COA reductase inhibitors with their pleiotropic effects are widely under investigation. METHOD: A comprehensive literature search on Scopus and PubMed databases was conducted using the keywords 'CCL2', 'CCR2', 'monocyte chemoattractant protein-1', 'HMG-COA reductase inhibitor', and 'statin'. Both experimental and clinical studies measuring CCL2/CCR2 expressions following statin therapy were identified excluding the ones focused on cardiovascular diseases. RESULTS: Herein, we summarized the effects of statins on CCL2 and CCR2 expression in various pathologic conditions including immune-mediated diseases, nephropathies, diabetes, rheumatic diseases, neuroinflammation, inflammatory bowel diseases, gynecologic diseases, and cancers. CONCLUSION: For the most part, statins play an inhibitory role on the CCL2-CCR2 axis which implies their potential to be further developed as therapeutic options in non-cardiovascular diseases either alone or in combination with other conventional treatments. However, the existing literature mostly focused on experimental models and is therefore inadequate to reach a conclusion.

The Therapeutic Potential of Targeting Key Signaling Pathways as a Novel Approach to Ameliorating Post-Surgical Adhesions.

BACKGROUND: Peritoneal adhesions (PA) are a common complication of abdominal operations. A growing body of evidence shows that inhibition of inflammation and fibrosis at sites of peritoneal damaging could prevent the development of intra-abdominal adhesions. METHODS: A search of PubMed, Medline, CINAHL and Embase databases was performed using the keywords 'postsurgical adhesion', 'post-operative adhesion', 'peritoneal adhesion', 'surgery-induced adhesion' and 'abdominal adhesion'. Studies detailing the use of pharmacological and non-pharmacological agents for peritoneal adhesion prevention were identified, and their bibliographies were thoroughly reviewed to identify further related articles. RESULTS: Several signaling pathways, such as tumor necrosis factor-alpha, tissue plasminogen activator, and type 1 plasminogen activator inhibitor, macrophages, fibroblasts, and mesothelial cells play a key part in the development of plasminogen activator. Several therapeutic approaches based on anti-PA drug barriers and traditional herbal medicines have been developed to prevent and treat adhesion formation. In recent years, the most promising method to prevent PA is treatment using biomaterial-based barriers. CONCLUSION: In this review, we provide an overview of the pathophysiology of adhesion formation and various agents targeting different pathways, including chemical agents, herbal agents, physical barriers, and clinical trials concerning this matter.