The Protective Effects of Aliskiren on Lung Histopathology after Triolein-Induced Fat Embolism Amanda Fletcher, 1,2 Alan Poisner, 1 Rakesh Ponnapureddy, 2 Chirag Patel, 2 Mark Pluym, 2 Simran Arora, 2 Agostino Molteni 2 1 University of Kansas Medical Center, Kansas City, KS; 2 UMKC School of Medicine, Kansas City, MO. INTRODUCTION It has been well demonstrated that the renin angiotensin system (RAS) plays a significant role in the pathophysiology of fat embolism (FE). The objective of this study is to assess the effects of a direct renin inhibitor, aliskiren, on lung histopathology following triolein-induced FE. METHODS Twenty-two rats were divided into four groups as seen in table 1. Group-A served as the controls. The remaining three groups (Group-B, Group-C, Group-D), underwent FE induction via triolein 0.2 mL i.v. at 0 hours, and at 1 hour were treated with saline 0.2 mL i.p., aliskiren 50 mg/kg i.p., and aliskiren 100 mg/kg i.p., respectively. Rats were euthanized at 48 hours and lungs stained with H&E for lumen patency measurements, Masson’s trichrome (MT) for collagen, and alpha-smooth muscle actin (SMA) for myofibroblasts, and Oil Red O for fat. RESULTS Fibrosis: Rats treated with triolein alone, group B, showed statistically significant fibrotic changes with increased collagen (Masson’s trichrome) and myofibroblast activation (  -SMA) compared to the others three groups (p < 0.01). Aliskiren blocked this inflammatory and fibrotic process by reducing the intensity of these stains to a level indistinguishable from the controls (p < 0.01). Fat: Rats treated with triolein alone, group B, showed a statistically significant increase in fat compared to the others three groups (p < 0.01). Aliskiren administration at both doses reduced the presence of fat to a level indistinguishable from the controls. Vessels: While not statistically significant, there was a trend in reduced lumen patency in Group-B which improved after aliskiren treatment. CONCLUSION/ CLINICAL IMPLICATIONS These results provide supportive evidence of the extensive involvement of the RAS in the pathology of FE and the ability of a renin inhibitor to mitigate this damage. Clinical implications include the use of aliskiren as both a prophylactic (before orthopedic procedures) and therapeutic (after severe trauma) treatment for FE to prevent the consequent severe pulmonary fibrosis. REFERENCES/ACKNOWLEDGEMENTS (1) Mary Katherine Geldmacher Research Foundation, St. Louis, MO (2) This work was supported by a CTSA grant from NCRR and NCATS awarded to the University of Kansas Medical Center for Frontiers: The Heartland Institute for Clinical and Translational Research # TL1TR The contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIH, NCRR, or NCATS. TABLE 1: TREATMENT REGIMEN GroupnDay 0, hr 0 Day 2, hr 48 A4Saline 0.2 mL i.v.Saline 0.2 mL i.p.Euthanasia B6Triolein 0.2 mL i.v.Saline 0.2 mL i.p.Euthanasia C6Triolein 0.2 mL i.v.Aliskiren 50 mg/kg i.p. Euthanasia D6Triolein 0.2 mL i.v.Aliskiren 100 mg/kg i.p. Euthanasia Controls Triolein(T) T+Aliskiren 50 T+Aliskiren 100 H&E Trichrome (collagen) Alpha-SMA Oil Red O (fat) Figure 1. Asterisks indicate a significant difference from the triolein group (p<0.01).