Reducing atherogenic lipoprotein-cholesterol by lowering hepatocyte PAI1

This dataset contains the primary experimental data, statistical analyses, and figure source files associated with the American Heart Association Collaborative Science Award, "Reducing Atherogenic Lipoprotein-Cholesterol by Lowering Hepatocyte PAI-1." The data support studies investigating the effects of hepatocyte PAI-1 knockdown on circulating PAI-1 levels, thrombosis, cholesterol metabolism, aging-related phenotypes, and treatment safety in mouse models. Dataset Contents Adobe Illustrator Figure Source Files (.ai) Figure 1.ai – Circulating PAI-1 can be knocked down with siRNA-lipid nanoparticles in mice. Figure 2.ai – siPAI-1 decreases thrombosis in both young and aged mice and improves survival in aged mice in the inferior vena cava (IVC) stasis model of venous thrombosis. Figure 3.ai – Hepatic PAI-1 mRNA expression is elevated in obese mice and can be normalized with siPAI-1. Figure 4.ai – Repeated administration of siPAI-1 consistently reduces circulating PAI-1 levels and prolongs lifespan in a fast-aging mouse model. Figure 5.ai – Knockdown of PAI-1 with siPAI-1 does not produce overt toxicity or increased bleeding in mice. Microsoft Excel Data Files (.xlsx) ELISA Data_10Apr25.xlsx ELISA Data_17Apr25.xlsx ELISA Data_13May24.xlsx ELISA Data_15Jul25.xlsx ELISA Data_25Jul25.xlsx ELISA Data_31Jul25.xlsx Toxicity Sample Data.xlsx Cholesterol Study.xlsx Primer Screen.xlsx RNA qPCR.xlsx qPCR for LNP Treated and Untreated Mice.xlsx Knockdown Screen.xlsx These files contain raw and processed ELISA, qPCR, cholesterol, toxicity, and screening data used in the associated analyses. GraphPad Prism Files (.prism or .pzfx) ELISA Standard Curve Plasmin Activity Assay Manuscript Data These files contain processed datasets, statistical analyses, graphical outputs, and figure generation workflows used for data visualization and manuscript preparation. Methods and Reuse Experimental data were generated from mouse studies evaluating the biological effects of hepatocyte PAI-1 knockdown using siRNA-lipid nanoparticle formulations. Excel files contain source data and assay results, GraphPad Prism files contain statistical analyses and graphing workflows, and Adobe Illustrator files contain editable publication-quality figure source files. Related Funding This dataset was generated with support from: American Heart Association (AHA), Collaborative Science Award #952422 National Institutes of Health (NIH), R01HL166382 Canadian Institutes of Health Research (CIHR), Doctoral Award #187577 (F.F.), Postdoctoral Fellowship #MFE181897 (W.S.H.), and Postdoctoral Fellowship #MFE414357 (C.L.)