Hydrogen Sulfide Modulation of Matrix Metalloproteinases and CD147/EMMPRIN: Mechanistic Pathways and Impact on Atherosclerosis Progression

Abstract

Atherosclerosis is a chronic inflammatory condition marked by endothelial dysfunction, lipid accumulation, inflammatory cell infiltration, and extracellular matrix (ECM) remodeling within arterial walls, leading to plaque formation and potential cardiovascular events. Key players in ECM remodeling and inflammation are matrix metalloproteinases (MMPs) and CD147/EMMPRIN, a cell surface glycoprotein expressed on endothelial cells, vascular smooth muscle cells (VSMCs), and immune cells, that regulates MMP activity. Hydrogen sulfide (H₂S), a gaseous signaling molecule, has emerged as a significant modulator of these processes including oxidative stress mitigation, inflammation reduction, and vascular remodeling. This systematic review investigates the mechanistic pathways through which H₂S influences MMPs and CD147/EMMPRIN and assesses its impact on atherosclerosis progression. A comprehensive literature search was conducted across PubMed, Scopus, and Web of Science databases, focusing on studies examining H₂S modulation of MMPs and CD147/EMMPRIN in atherosclerosis contexts. Findings indicate that H₂S modulates MMP expression and activity through transcriptional regulation and post-translational modifications, including S-sulfhydration. By mitigating oxidative stress, H₂S reduces MMP activation, contributing to plaque stability and vascular remodeling. H₂S also downregulates CD147/EMMPRIN expression via transcriptional pathways, diminishing inflammatory responses and vascular cellular proliferation within plaques. The dual regulatory role of H₂S in inhibiting MMP activity and downregulating CD147 suggests its potential as a therapeutic agent in stabilizing atherosclerotic plaques and mitigating inflammation. Further research is warranted to elucidate the precise molecular mechanisms and to explore H₂S-based therapies for clinical application in atherosclerosis.

Keywords

• hydrogen sulfide (H₂S)
• matrix metalloproteinases (MMPs)
• CD147/EMMPRIN
• atherosclerosis
• inflammation
• vascular remodeling