Acute respiratory distress syndrome leads to reduced ratio of ACE/ACE2 activities and is prevented by angiotensin-(1-7) or an angiotensin II receptor antagonist

Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome. Angiotensin‐converting enzyme (ACE) and its effector peptide angiotensin (Ang) II have been implicated in the pathogenesis of ARDS. A counter‐regulatory enzyme of ACE, ie ACE2 that degrades Ang II to Ang‐(1–7), offers a p...

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Vydáno v:	The Journal of pathology Ročník 225; číslo 4; s. 618 - 627
Hlavní autoři:	Wösten-van Asperen, Roelie M, Lutter, René, Specht, Patricia A, Moll, Gert N, van Woensel, Job B, van der Loos, Chris M, van Goor, Harry, Kamilic, Jelena, Florquin, Sandrine, Bos, Albert P
Médium:	Journal Article
Jazyk:	angličtina
Vydáno:	Chichester, UK John Wiley & Sons, Ltd 01.12.2011 Wiley
Témata:	acute lung injury Angiotensin I - pharmacology angiotensin II Angiotensin Receptor Antagonists - pharmacology angiotensin-(1-7) Animals Biological and medical sciences Bronchoalveolar Lavage Fluid - chemistry cytokines Disease Models, Animal Intubation, Intratracheal Investigative techniques, diagnostic techniques (general aspects) Lipopolysaccharides - analysis Losartan - pharmacology Lung - drug effects Lung - pathology Macrophages, Alveolar - drug effects Macrophages, Alveolar - enzymology Macrophages, Alveolar - pathology Male Medical sciences Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques Peptide Fragments - pharmacology Peptidyl-Dipeptidase A - analysis Peptidyl-Dipeptidase A - metabolism Rats Rats, Sprague-Dawley Respiratory Distress Syndrome, Adult - chemically induced Respiratory Distress Syndrome, Adult - enzymology Respiratory Distress Syndrome, Adult - pathology Lung disease Respiratory disease Acute Cytokine acute lung injury Biological activity Heavy metal Prevention Renin angiotensin system Anatomic pathology Adult respiratory distress syndrome Lead angiotensin-(1-7) Ratio cytokines Angiotensin antagonist Angiotensin II Biological receptor
ISSN:	0022-3417, 1096-9896, 1096-9896
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Popis
Shrnutí:	Acute respiratory distress syndrome (ARDS) is a devastating clinical syndrome. Angiotensin‐converting enzyme (ACE) and its effector peptide angiotensin (Ang) II have been implicated in the pathogenesis of ARDS. A counter‐regulatory enzyme of ACE, ie ACE2 that degrades Ang II to Ang‐(1–7), offers a promising novel treatment modality for this syndrome. As the involvement of ACE and ACE2 in ARDS is still unclear, this study investigated the role of these two enzymes in an animal model of ARDS. ARDS was induced in rats by intratracheal administration of LPS followed by mechanical ventilation. During ventilation, animals were treated with saline (placebo), losartan (Ang II receptor antagonist), or with a protease‐resistant, cyclic form of Ang‐(1–7) [cAng‐(1–7)]. In bronchoalveolar lavage fluid (BALF) of ventilated LPS‐exposed animals, ACE activity was enhanced, whereas ACE2 activity was reduced. This was matched by enhanced BALF levels of Ang II and reduced levels of Ang‐(1–7). Therapeutic intervention with cAng‐(1–7) attenuated the inflammatory mediator response, markedly decreased lung injury scores, and improved lung function, as evidenced by increased oxygenation. These data indicate that ARDS develops, in part, due to reduced pulmonary levels of Ang‐(1–7) and that repletion of this peptide halts the development of ARDS. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.
Bibliografie:	Supporting Information: Figure S1. Dose response experiments of cyclic Ang-(1-7).Supporting Information: Figure S2. Single antibody staining for Ang II type 1 receptor (AT1; developed by Vector Blue), the Mas receptor [for Ang-(1-7); developed by diaminobenzidine], and the epithelial cell marker AE1/AE3 and macrophage marker ED-1 (developed by Vector Red) in unexposed and LPS-exposed mechanically ventilated animals.Supporting Information: Legends to Figure S2 ark:/67375/WNG-0TT80B67-M istex:1DCEC6C2F0D85CFD69C0E473B62B12D0D6D7AA56 No conflicts of interest were declared. ArticleID:PATH2987 These authors contributed equally to this study. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	0022-3417 1096-9896 1096-9896
DOI:	10.1002/path.2987