Dichotomous Roles of Smooth Muscle Cell–Derived MCP1 (Monocyte Chemoattractant Protein 1) in Development of Atherosclerosis

• DOI: 10.1161/atvbaha.122.317882
• Publication Date: 2022-06-23T09:00:16Z
• Authors: Katherine M. Owsiany; Rebecca A. Deaton; Karen G. Soohoo; Anh Tram Nguyen; Gary K. Owens
• Keywords: Monocyte; Pathogenesis

Background: Smooth muscle cells (SMCs) in atherosclerotic plaque take on multiple nonclassical phenotypes that may affect stability and, therefore, the likelihood of myocardial infarction or stroke. However, mechanisms by which these are only beginning to be explored. Methods: In this study, we investigated contribution inflammatory MCP1 (monocyte chemoattractant protein 1) produced both classical Myh11 (myosin heavy chain 11) + SMCs and have transitioned through an Lgals3 (galectin 3) state atherosclerosis using smooth lineage tracing mice label all a dual system targets Lgals3-transitioned SMC only. Results: We show loss results paradoxical increase size macrophage content, driven baseline systemic monocytosis early pathogenesis. contrast, knockout complex resulted lesions with increased Acta2 (actin alpha 2, muscle) fibrous cap decreased investment SMCs, consistent stability. Finally, flow cytometry single-cell RNA sequencing, influences populations late-stage plaques. Conclusions: monocyte levels disease was atheroprotective, while subset exacerbated pathogenesis disease. Results first determine function highlight need for caution when considering therapeutic interventions involving MCP1.