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Browse ATS 2021 Abstracts

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ATS 2021 will feature presentations of original research from accepted abstracts. Mini Symposia and Thematic Poster Sessions are abstract based sessions.

Please use the form below to browse scientific abstracts and case reports accepted for ATS 2021. Abstracts presented at the ATS 2021 will be published in the Online Abstract Issue of the American Journal of Respiratory and Critical Care Medicine, Volume 203, May 3, 2021.

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Angiotensin (Ang-1-7) and Its Glycopeptide PNA5 Protect Against Overzealous Pulmonary Inflammation to Infectious and Non-Infectious Respiratory Insults

Session Title
TP113 - TP113 ACUTE LUNG INJURY AND REPAIR
Abstract
A4364 - Angiotensin (Ang-1-7) and Its Glycopeptide PNA5 Protect Against Overzealous Pulmonary Inflammation to Infectious and Non-Infectious Respiratory Insults
Author Block: J. G. Ledford1, K. Collins1, U. Younis2, R. Polt3, M. Hay4, H. M. Mansour5; 1Cellular & Molecular Medicine, University of Arizona, Tucson, AZ, United States, 2University of Arizona, Tucson, AZ, United States, 3Chemistry and Biochemistry, University of Arizona, Tucson, AZ, United States, 4Physiology, University of Arizona, Tucson, AZ, United States, 5Colleges of Pharmacy & Medicine, The University of Arizona, Tucson, AZ, United States.
RATIONALE: The peptide hormone angiotensin (Ang-(1-7)) has well-known anti-inflammatory protective effects, inhibiting production and expression of many cytokines and adhesion molecules that are associated with a “cytokine storm.” Recent reports suggest that ARDS appears to be a significant predictor of mortality and the COVID-19-induced “cytokine storm” is associated with increased morbidity and mortality. PNA5, a more stable, longer acting, and more brain penetrant glycopeptide analog of Ang-(1-7), has been developed to control inflammation. Our studies were developed to test if Ang-(1-7) and its glycopeptide PNA5 were protective in the lung against overzealous immune responses to infectious and non-infectious respiratory stimuli. METHODS: Wild type mice were treated with infectious or non-infectious agents: Mycoplasma pneumoniae (1x108, intranasal) or LPS (5 mg/kg body weight, oropharyngeal). Within 2 hrs of challenge, a subset of each was given either Ang-(1-7), PNA5, or peptide-free vehicle via different routes of administration: oropharyngeal or subcutaneous. Markers of inflammation in the lung were assessed within 72 hrs for each set of animals. RESULTS: During Mycoplasma infection, one high dose of Ang-(1-7) delivered to the lungs reduced neutrophilia and Muc5AC, as well as TNF-α and keratinocyte chemoattractant (KC). In line with severe COVID-related ARDS, a single dose of the Ang-(1-7) analog, PNA5, delivered subcutaneously to LPS-challenged mice led to significant protection against key features of ARDS: vascular permeability and pulmonary edema, neutrophil influx into the lung and TNF-α production. CONCLUSIONS: Ang1-7 has been shown by others to play a protective role to a variety of stimuli in a myriad of organs. Our new findings demonstrate that Ang1-7 and PNA5 can protect against both live Mp and LPS-induced lung inflammation. Replacement of Ang-(1-7) in ALI/ARDS patients, including severe COVD-19 patients, with an Ang-(1-7) replacement peptide such as PNA5, could be ideal adjunctive therapy to treat ALI/ARDS and support lung health and organ protection.