Angiotensin-converting enzyme 2 protects from severe acute lung failure
Identifieur interne : 000614 ( PascalFrancis/Corpus ); précédent : 000613; suivant : 000615Angiotensin-converting enzyme 2 protects from severe acute lung failure
Auteurs : Yumiko Imai ; Keiji Kuba ; SHUAN RAO ; YI HUAN ; FENG GUO ; BIN GUAN ; PENG YANG ; Renu Sarao ; Teiji Wada ; Howard Leong-Poi ; Michael A. Crackower ; Akiyoshi Fukamizu ; Chi-Chung Hui ; Lutz Hein ; Stefan Uhlig ; Arthur S. Slutsky ; CHENGYU JIANG ; Josef M. PenningerSource :
- Nature : (London) [ 0028-0836 ] ; 2005.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is a devastating clinical syndrome with a high mortality rate (30-60%) (refs 1-3). Predisposing factors for ARDS are diverse1,3 and include sepsis, aspiration, pneumonias and infections with the severe acute respiratory syndrome (SARS) coronavirus4,5. At present, there are no effective drugs for improving the clinical outcome of ARDS1-3. Angiotensin-converting enzyme (ACE) and ACE2 are homologues with different key functions in the renin-angiotensin system6-8. ACE cleaves angiotensin I to generate angiotensin II, whereas ACE2 inactivates angiotensin II and is a negative regulator of the system. ACE2 has also recently been identified as a potential SARS virus receptor and is expressed in lungs9,10. Here we report that ACE2 and the angiotensin II type 2 receptor (AT2) protect mice from severe acute lung injury induced by acid aspiration or sepsis. However, other components of the renin-angiotensin system, including ACE, angiotensin II and the angiotensin II type la receptor (AT1a), promote disease pathogenesis, induce lung oedemas and impair lung function. We show that mice deficient for Ace show markedly improved disease, and also that recombinant ACE2 can protect mice from severe acute lung injury. Our data identify a critical function for ACE2 in acute lung injury, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year.
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Format Inist (serveur)
NO : | PASCAL 05-0401946 INIST |
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ET : | Angiotensin-converting enzyme 2 protects from severe acute lung failure |
AU : | IMAI (Yumiko); KUBA (Keiji); SHUAN RAO; YI HUAN; FENG GUO; BIN GUAN; PENG YANG; SARAO (Renu); WADA (Teiji); LEONG-POI (Howard); CRACKOWER (Michael A.); FUKAMIZU (Akiyoshi); HUI (Chi-Chung); HEIN (Lutz); UHLIG (Stefan); SLUTSKY (Arthur S.); CHENGYU JIANG; PENNINGER (Josef M.) |
AF : | MBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences/Vienna 1030/Autriche (1 aut., 2 aut., 8 aut., 9 aut., 18 aut.); National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College/Beijing 100005/Chine (3 aut., 4 aut., 5 aut., 6 aut., 7 aut., 17 aut.); Department of Cardiology, St. Michael's Hospital/Toronto, Ontario MSB 1W8/Canada (10 aut.); Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research/Montreal, Quebec H3R 4P8/Canada (11 aut.); Center for Tsukuba Advanced Research Alliance, University of Tsukuba/Tsukuba 305-8577/Japon (12 aut.); Program in Developmental Biology, The Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto/Toronto, Ontario MG5 1X8/Canada (13 aut.); Department of Pharmacology, University of Freiburg/Freiburg 79104/Allemagne (14 aut.); Division of Pulmonary Pharmacology, Research Center Borstel/Borstel 23845/Allemagne (15 aut.); Department of Medicine and Interdepartmental Division of Critical Care, University of Toronto, St. Michael's Hospital/Toronto, Ontario MSB 1W8/Canada (16 aut.) |
DT : | Publication en série; Correspondance, lettre; Niveau analytique |
SO : | Nature : (London); ISSN 0028-0836; Coden NATUAS; Royaume-Uni; Da. 2005; Vol. 436; No. 7047; Pp. 112-116; Bibl. 30 ref. |
LA : | Anglais |
EA : | Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is a devastating clinical syndrome with a high mortality rate (30-60%) (refs 1-3). Predisposing factors for ARDS are diverse1,3 and include sepsis, aspiration, pneumonias and infections with the severe acute respiratory syndrome (SARS) coronavirus4,5. At present, there are no effective drugs for improving the clinical outcome of ARDS1-3. Angiotensin-converting enzyme (ACE) and ACE2 are homologues with different key functions in the renin-angiotensin system6-8. ACE cleaves angiotensin I to generate angiotensin II, whereas ACE2 inactivates angiotensin II and is a negative regulator of the system. ACE2 has also recently been identified as a potential SARS virus receptor and is expressed in lungs9,10. Here we report that ACE2 and the angiotensin II type 2 receptor (AT2) protect mice from severe acute lung injury induced by acid aspiration or sepsis. However, other components of the renin-angiotensin system, including ACE, angiotensin II and the angiotensin II type la receptor (AT1a), promote disease pathogenesis, induce lung oedemas and impair lung function. We show that mice deficient for Ace show markedly improved disease, and also that recombinant ACE2 can protect mice from severe acute lung injury. Our data identify a critical function for ACE2 in acute lung injury, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year. |
CC : | 002B05C02C |
FD : | Syndrome respiratoire aigu sévère; Homme; Détresse respiratoire; Etiologie; Peptidyl-dipeptidase A; Inhibiteur angiotensin converting enzyme; Animal; Souris; Protéine recombinante; Chimiothérapie; ACE2 |
FG : | Virose; Infection; Peptidyl-dipeptidases; Peptidases; Hydrolases; Enzyme; Rodentia; Mammalia; Vertebrata |
ED : | Severe acute respiratory syndrome; Human; Respiratory distress; Etiology; Peptidyl-dipeptidase A; ACE inhibitor; Animal; Mouse; Recombinant protein; Chemotherapy |
EG : | Viral disease; Infection; Peptidyl-dipeptidases; Peptidases; Hydrolases; Enzyme; Rodentia; Mammalia; Vertebrata |
SD : | Síndrome respiratorio agudo severo; Hombre; Trastorno respiratorio; Etiología; Peptidyl-dipeptidase A; Inhibidor angiotensin converting enzyme; Animal; Ratón; Proteína recombinante; Quimioterapia |
LO : | INIST-142.354000138281660220 |
ID : | 05-0401946 |
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Pascal:05-0401946Le document en format XML
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<sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Angiotensin-converting enzyme 2 protects from severe acute lung failure</title>
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<author><name sortKey="Chengyu Jiang" sort="Chengyu Jiang" uniqKey="Chengyu Jiang" last="Chengyu Jiang">CHENGYU JIANG</name>
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<front><div type="abstract" xml:lang="en">Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is a devastating clinical syndrome with a high mortality rate (30-60%) (refs 1-3). Predisposing factors for ARDS are diverse<sup>1,3</sup>
and include sepsis, aspiration, pneumonias and infections with the severe acute respiratory syndrome (SARS) coronavirus<sup>4,5</sup>
. At present, there are no effective drugs for improving the clinical outcome of ARDS<sup>1-3</sup>
. Angiotensin-converting enzyme (ACE) and ACE2 are homologues with different key functions in the renin-angiotensin system<sup>6-8</sup>
. ACE cleaves angiotensin I to generate angiotensin II, whereas ACE2 inactivates angiotensin II and is a negative regulator of the system. ACE2 has also recently been identified as a potential SARS virus receptor and is expressed in lungs<sup>9,10</sup>
. Here we report that ACE2 and the angiotensin II type 2 receptor (AT<sub>2</sub>
) protect mice from severe acute lung injury induced by acid aspiration or sepsis. However, other components of the renin-angiotensin system, including ACE, angiotensin II and the angiotensin II type la receptor (AT<sub>1</sub>
a), promote disease pathogenesis, induce lung oedemas and impair lung function. We show that mice deficient for Ace show markedly improved disease, and also that recombinant ACE2 can protect mice from severe acute lung injury. Our data identify a critical function for ACE2 in acute lung injury, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year.</div>
</front>
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<fA08 i1="01" i2="1" l="ENG"><s1>Angiotensin-converting enzyme 2 protects from severe acute lung failure</s1>
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<fA14 i1="04"><s1>Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research</s1>
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<fA14 i1="09"><s1>Department of Medicine and Interdepartmental Division of Critical Care, University of Toronto, St. Michael's Hospital</s1>
<s2>Toronto, Ontario MSB 1W8</s2>
<s3>CAN</s3>
<sZ>16 aut.</sZ>
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and include sepsis, aspiration, pneumonias and infections with the severe acute respiratory syndrome (SARS) coronavirus<sup>4,5</sup>
. At present, there are no effective drugs for improving the clinical outcome of ARDS<sup>1-3</sup>
. Angiotensin-converting enzyme (ACE) and ACE2 are homologues with different key functions in the renin-angiotensin system<sup>6-8</sup>
. ACE cleaves angiotensin I to generate angiotensin II, whereas ACE2 inactivates angiotensin II and is a negative regulator of the system. ACE2 has also recently been identified as a potential SARS virus receptor and is expressed in lungs<sup>9,10</sup>
. Here we report that ACE2 and the angiotensin II type 2 receptor (AT<sub>2</sub>
) protect mice from severe acute lung injury induced by acid aspiration or sepsis. However, other components of the renin-angiotensin system, including ACE, angiotensin II and the angiotensin II type la receptor (AT<sub>1</sub>
a), promote disease pathogenesis, induce lung oedemas and impair lung function. We show that mice deficient for Ace show markedly improved disease, and also that recombinant ACE2 can protect mice from severe acute lung injury. Our data identify a critical function for ACE2 in acute lung injury, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year.</s0>
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<server><NO>PASCAL 05-0401946 INIST</NO>
<ET>Angiotensin-converting enzyme 2 protects from severe acute lung failure</ET>
<AU>IMAI (Yumiko); KUBA (Keiji); SHUAN RAO; YI HUAN; FENG GUO; BIN GUAN; PENG YANG; SARAO (Renu); WADA (Teiji); LEONG-POI (Howard); CRACKOWER (Michael A.); FUKAMIZU (Akiyoshi); HUI (Chi-Chung); HEIN (Lutz); UHLIG (Stefan); SLUTSKY (Arthur S.); CHENGYU JIANG; PENNINGER (Josef M.)</AU>
<AF>MBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences/Vienna 1030/Autriche (1 aut., 2 aut., 8 aut., 9 aut., 18 aut.); National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College/Beijing 100005/Chine (3 aut., 4 aut., 5 aut., 6 aut., 7 aut., 17 aut.); Department of Cardiology, St. Michael's Hospital/Toronto, Ontario MSB 1W8/Canada (10 aut.); Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research/Montreal, Quebec H3R 4P8/Canada (11 aut.); Center for Tsukuba Advanced Research Alliance, University of Tsukuba/Tsukuba 305-8577/Japon (12 aut.); Program in Developmental Biology, The Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto/Toronto, Ontario MG5 1X8/Canada (13 aut.); Department of Pharmacology, University of Freiburg/Freiburg 79104/Allemagne (14 aut.); Division of Pulmonary Pharmacology, Research Center Borstel/Borstel 23845/Allemagne (15 aut.); Department of Medicine and Interdepartmental Division of Critical Care, University of Toronto, St. Michael's Hospital/Toronto, Ontario MSB 1W8/Canada (16 aut.)</AF>
<DT>Publication en série; Correspondance, lettre; Niveau analytique</DT>
<SO>Nature : (London); ISSN 0028-0836; Coden NATUAS; Royaume-Uni; Da. 2005; Vol. 436; No. 7047; Pp. 112-116; Bibl. 30 ref.</SO>
<LA>Anglais</LA>
<EA>Acute respiratory distress syndrome (ARDS), the most severe form of acute lung injury, is a devastating clinical syndrome with a high mortality rate (30-60%) (refs 1-3). Predisposing factors for ARDS are diverse<sup>1,3</sup>
and include sepsis, aspiration, pneumonias and infections with the severe acute respiratory syndrome (SARS) coronavirus<sup>4,5</sup>
. At present, there are no effective drugs for improving the clinical outcome of ARDS<sup>1-3</sup>
. Angiotensin-converting enzyme (ACE) and ACE2 are homologues with different key functions in the renin-angiotensin system<sup>6-8</sup>
. ACE cleaves angiotensin I to generate angiotensin II, whereas ACE2 inactivates angiotensin II and is a negative regulator of the system. ACE2 has also recently been identified as a potential SARS virus receptor and is expressed in lungs<sup>9,10</sup>
. Here we report that ACE2 and the angiotensin II type 2 receptor (AT<sub>2</sub>
) protect mice from severe acute lung injury induced by acid aspiration or sepsis. However, other components of the renin-angiotensin system, including ACE, angiotensin II and the angiotensin II type la receptor (AT<sub>1</sub>
a), promote disease pathogenesis, induce lung oedemas and impair lung function. We show that mice deficient for Ace show markedly improved disease, and also that recombinant ACE2 can protect mice from severe acute lung injury. Our data identify a critical function for ACE2 in acute lung injury, pointing to a possible therapy for a syndrome affecting millions of people worldwide every year.</EA>
<CC>002B05C02C</CC>
<FD>Syndrome respiratoire aigu sévère; Homme; Détresse respiratoire; Etiologie; Peptidyl-dipeptidase A; Inhibiteur angiotensin converting enzyme; Animal; Souris; Protéine recombinante; Chimiothérapie; ACE2</FD>
<FG>Virose; Infection; Peptidyl-dipeptidases; Peptidases; Hydrolases; Enzyme; Rodentia; Mammalia; Vertebrata</FG>
<ED>Severe acute respiratory syndrome; Human; Respiratory distress; Etiology; Peptidyl-dipeptidase A; ACE inhibitor; Animal; Mouse; Recombinant protein; Chemotherapy</ED>
<EG>Viral disease; Infection; Peptidyl-dipeptidases; Peptidases; Hydrolases; Enzyme; Rodentia; Mammalia; Vertebrata</EG>
<SD>Síndrome respiratorio agudo severo; Hombre; Trastorno respiratorio; Etiología; Peptidyl-dipeptidase A; Inhibidor angiotensin converting enzyme; Animal; Ratón; Proteína recombinante; Quimioterapia</SD>
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