Abstract 452: Contribution Of Smooth Muscle-derived Vascular Progenitor Cells To Atherosclerosis

• DOI: 10.1161/atvb.43.suppl_1.452
• Publication Date: 2023-10-02T14:09:33Z
• Authors: Allison M Dubner; Sizhao Lu; Austin Jolly; Tysen Noble; Raphael Nemenoff; Karen Moulton; Mary C Weiser-Evans
• Keywords: KLF4; Pericyte; Mural cell; Myofibroblast; Multipotent Stem Cell

Purpose: Atherosclerosis is a major cause of morbidity and mortality worldwide, but current therapies fail to adequately meet clinical needs. Our group discovered unique population adventitial multipotent resident vascular stem cells (AdvSca1-SM cells) that derive from mature smooth muscle (SMCs) are poised respond injury. The goal this project was determine the role AdvSca1-SM in setting atherosclerosis. We hypothesized contribute plaque growth or neovascularization drive disease progression. Methods: Highly specific cell-specific lineage tracing mice were placed on either normal chow given PCSK9 AAV injections induce LDLR KO high fat/high cholesterol diet for 8 30 weeks. vasculature analyzed using scRNA-Seq, immunofluorescence microscopy, flow cytometry. Results: scRNA-Seq cytometry revealed large reservoir stem-like state atherosclerosis, which expected focal nature formation. However, significant phenotypic shifts observed compared conditions. Additionally, knockout stemness-associated transcription factor Klf4 altered phenotype non-AdvSca1-SM-derived cells, indicating signaling other microenvironment. also differentiated predominantly into SMCs, modulated myofibroblasts, found core plaque, fibrous cap, medial wall. Finally, these be associated with microvessels regions, supporting neovascularization. Conclusions: These studies emphasize dynamic chronic hyperlipidemia-induced demonstrating potential both differentiate variety cell types as well signal Ongoing characterizing distinct contributions