Abstract 102: Hyperlipidemia-induced Hematopoiesis is Repressed by MLKL in Endothelial Cells of the Splenic Niche

• DOI: 10.1161/atvb.43.suppl_1.102
• Publication Date: 2023-10-02T14:09:33Z
• Authors: Adil Rasheed; Taylor Dennison; Sabrina Robichaud; Hailey Wyatt; My-Anh Nguyen; Michele Geoffrion; Yacine Marouf; Adir Baxi; Richard Lee; Hilal Kazan; Coen van Solingen; Mireille I Ouimet; Katey J Rayner
• Keywords: 0301 basic medicine; 03 medical and health sciences; 3. Good health

The mixed lineage kinase domain-like protein (MLKL) is well-known for its role in the execution of necroptotic cell death. We showed that antisense oligonucleotide knockdown MLKL ( Mlkl KD) Apoe -knockout mice reduces plaque necrotic core, as predicted, but not total area. Additionally, KD expanded splenic hematopoietic stem and progenitor cells (HSPCs) mature myeloid known to drive atherogenesis. Thus, we hypothesized limits hematopoiesis thereby immune contributions growing atheroma. To test whether or non-hematopoietic expression was responsible HSPC expansion, transplanted Ldlr with bone marrow found no changes hematopoiesis, suggesting functions other niche. Flow cytometry immunofluorescence staining during a time course atherosclerosis revealed decrease endothelial correlated reduction endogenously by KD, maintains cells. Both vivo vitro observed increased lipid accumulation concomitant defects cycle Similar our previous work macrophages, led an CHMP4B cultured cells, aberrant endocytic trafficking, which has also been linked dysfunctional proliferation. Furthermore, there greater production derived from CD45.1 HSPCs recipient spleens. Co-culture pStat5, marker activation, coupled increase colony formation, compared co-culture control Remarkably regulation were upon In conclusion, demonstrate novel regulating balance HSPCs, specifically through preservation repress highlighting importance spleen metabolism impact on inflammation potentiates