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Diffuse Lung Disease |

The Renin-Angiotensin System [RAS] in Fat Embolism-Induced Lung Pathology

Ammar Alkhazna, MD; Anwaar Saeed, MD; Betty Herndon, PhD; Amna Hilal, BS; Tim Quinn, BS; Agostino Molteni, PhD; Gary Salzman, MD
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University of Missouri - Kansas City, Kansas City, MO


Chest. 2013;144(4_MeetingAbstracts):463A. doi:10.1378/chest.1703841
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Abstract

SESSION TITLE: Cytokines/Cellular Interactions Posters

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 30, 2013 at 01:30 PM - 02:30 PM

PURPOSE: Angiotensin (1-7) [Ang 1-7] plays a beneficial role by preventing and reversing pulmonary hypertension and fibrosis related to Angiotensin II [Ang II] in fat embolism (FE) following major bone fractures. Our objective is to study the interactions of the RAS and FE using an animal model.

METHODS: To evaluate lung effects of RAS in FE, 60 outbred rats were administered either 0.2 mL triolein i.v. or saline; subgroups of both received 50 mg/kg captopril i.p. or 10 mg/kg losartan 1 hr after triolein. At 24-94 hr, lungs were fixed for histology or frozen for homogenization, peptide purification (C-18 columns) and tested by ELISAs for Ang II and for Ang 1-7. All lungs were stained for smooth muscle actin (SMA) and H&E. Pro-fibrotic area (SMA stain vs counterstain) was quantified using Image analysis.

RESULTS: SMA staining increased in FE models (3.4% ± 1.3) over controls (1.9 ± 0.89). Ang II in lungs after FE increased from 24 hr (p: 0.049) to 96 hr (p: 0.062), both increased over controls. Though both drugs improved pulmonary histology in vivo, the lung Ang II peptides in drug-treated animals increased to 0.14 - 0.17 at 48 hr p=0.001. To resolve the in vitro-in vivo differences, Ang 1-7 was evaluated in these lungs, showing minor change with the drug treatments. Recent research attributes much of the Ang 1-7 activity to its receptor Mas in some organs.

CONCLUSIONS: In a model of triolein-induced lung injury (FE), inflammation and fibrosis were inhibited by drugs acting at different sites in the RAS. In vitro differences in Ang II and Ang 1-7 peptides in rat lungs, evaluated by ELISA, suggests local counter regulation. Progress continues in evaluating RAS components in this model.

CLINICAL IMPLICATIONS: Dissecting the mechanisms involved in a fat embolism model offers a potential strategy for both orthopedic and pulmonary progress in antifibrotic therapy in FE.

DISCLOSURE: The following authors have nothing to disclose: Ammar Alkhazna, Anwaar Saeed, Betty Herndon, Amna Hilal, Tim Quinn, Agostino Molteni, Gary Salzman

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