Abstract We075: Stimulator of Interferon Genes (STING) Regulates T Cell Fate in Cardiometabolic Heart Failure with Preserved Ejection Fraction (HFpEF)

• DOI: 10.1161/res.135.suppl_1.we075
• Publication Date: 2024-10-09T14:03:28Z
• Authors: Sasha Smolgovsky; Abraham Bayer; Ramona Emig; Zoie Magri; mark aronovitz; Kuljeet kaur; Alexander Poltorak; Robert Blanton; Pilar Alcaide
• Keywords: Sting

Introduction: Combined obesity and hypertension alter the endoplasmic reticulum (ER) stress response by downregulating X-box binding protein 1 ( Xbp1 ) in T cells, which heightens cell inflammatory potential persistence Heart Failure with Preserved Ejection Fraction (HFpEF), a prevalent syndrome no cure. The ER Stimulator of Interferon Genes (STING), concert , coordinates inflammation death other contexts, yet its role cardiometabolic HFpEF is unknown. Hypothesis: STING activation dysregulated responses drive balancing to combined comorbidities. Methods: C67BL/6J (wild type, WT) mice were fed high-fat diet/L-NAME (H/L) or standard chow (STD) for 5 weeks, was measured splenic CD4 + cells Western blotting. Splenic from WT STING-deficient (STING -/- activated αCD3/αCD28 3 days vitro then treated complete media (CM) CM 0.2 mM palmitate (abundant dietary fat)/0.2 L-NAME (PALNA) up 48 hours. gene expression, activation, assessed using qPCR, flow cytometry, blotting, Lionheart live-cell microscopy. Results: Mice H/L had significantly increased expression phospho-STING, alongside decreased cardiac inflammation, compared STD-fed mice. Ex vivo incubation PALNA apoptosis, indicated cleaved caspase-3 poly (ADP-ribose) polymerase (PARP) CM. However, remaining live PALNA-treated showed higher CD69, this sustained over time, Strikingly, imaging revealed that improved survival CD69 cells. Conclusions: contributes experimental synergizing promote emergence hyperactivated