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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Crackower</name><affiliation><inist:fA14 i1="04"><s1>Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research</s1><s2>Montreal, Quebec H3R 4P8</s2><s3>CAN</s3><sZ>11 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Fukamizu, Akiyoshi" sort="Fukamizu, Akiyoshi" uniqKey="Fukamizu A" first="Akiyoshi" last="Fukamizu">Akiyoshi Fukamizu</name><affiliation><inist:fA14 i1="05"><s1>Center for Tsukuba Advanced Research Alliance, University of Tsukuba</s1><s2>Tsukuba 305-8577</s2><s3>JPN</s3><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hui, Chi Chung" sort="Hui, Chi Chung" uniqKey="Hui C" first="Chi-Chung" last="Hui">Chi-Chung Hui</name><affiliation><inist:fA14 i1="06"><s1>Program in Developmental Biology, The Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto</s1><s2>Toronto, Ontario MG5 1X8</s2><s3>CAN</s3><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hein, Lutz" sort="Hein, Lutz" uniqKey="Hein L" first="Lutz" last="Hein">Lutz Hein</name><affiliation><inist:fA14 i1="07"><s1>Department of Pharmacology, University of Freiburg</s1><s2>Freiburg 79104</s2><s3>DEU</s3><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Uhlig, Stefan" sort="Uhlig, Stefan" uniqKey="Uhlig S" first="Stefan" last="Uhlig">Stefan Uhlig</name><affiliation><inist:fA14 i1="08"><s1>Division of Pulmonary Pharmacology, Research Center Borstel</s1><s2>Borstel 23845</s2><s3>DEU</s3><sZ>15 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Slutsky, Arthur S" sort="Slutsky, Arthur S" uniqKey="Slutsky A" first="Arthur S." last="Slutsky">Arthur S. Slutsky</name><affiliation><inist: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></inist:fA14></affiliation></author><author><name sortKey="Chengyu Jiang" sort="Chengyu Jiang" uniqKey="Chengyu Jiang" last="Chengyu Jiang">CHENGYU JIANG</name><affiliation><inist:fA14 i1="02"><s1>National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College</s1><s2>Beijing 100005</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Penninger, Josef M" sort="Penninger, Josef M" uniqKey="Penninger J" first="Josef M." last="Penninger">Josef M. Penninger</name><affiliation><inist:fA14 i1="01"><s1>MBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences</s1><s2>Vienna 1030</s2><s3>AUT</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">05-0401946</idno><date when="2005">2005</date><idno type="stanalyst">PASCAL 05-0401946 INIST</idno><idno type="RBID">Pascal:05-0401946</idno><idno type="wicri:Area/PascalFrancis/Corpus">000614</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Angiotensin-converting enzyme 2 protects from severe acute lung failure</title><author><name sortKey="Imai, Yumiko" sort="Imai, Yumiko" uniqKey="Imai Y" first="Yumiko" last="Imai">Yumiko Imai</name><affiliation><inist:fA14 i1="01"><s1>MBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences</s1><s2>Vienna 1030</s2><s3>AUT</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Kuba, Keiji" sort="Kuba, Keiji" uniqKey="Kuba K" first="Keiji" last="Kuba">Keiji Kuba</name><affiliation><inist:fA14 i1="01"><s1>MBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences</s1><s2>Vienna 1030</s2><s3>AUT</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Shuan Rao" sort="Shuan Rao" uniqKey="Shuan Rao" last="Shuan Rao">SHUAN RAO</name><affiliation><inist:fA14 i1="02"><s1>National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College</s1><s2>Beijing 100005</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Yi Huan" sort="Yi Huan" uniqKey="Yi Huan" last="Yi Huan">YI HUAN</name><affiliation><inist:fA14 i1="02"><s1>National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College</s1><s2>Beijing 100005</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Feng Guo" sort="Feng Guo" uniqKey="Feng Guo" last="Feng Guo">FENG GUO</name><affiliation><inist:fA14 i1="02"><s1>National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College</s1><s2>Beijing 100005</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Bin Guan" sort="Bin Guan" uniqKey="Bin Guan" last="Bin Guan">BIN GUAN</name><affiliation><inist:fA14 i1="02"><s1>National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College</s1><s2>Beijing 100005</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Peng Yang" sort="Peng Yang" uniqKey="Peng Yang" last="Peng Yang">PENG YANG</name><affiliation><inist:fA14 i1="02"><s1>National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College</s1><s2>Beijing 100005</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Sarao, Renu" sort="Sarao, Renu" uniqKey="Sarao R" first="Renu" last="Sarao">Renu Sarao</name><affiliation><inist:fA14 i1="01"><s1>MBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences</s1><s2>Vienna 1030</s2><s3>AUT</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Wada, Teiji" sort="Wada, Teiji" uniqKey="Wada T" first="Teiji" last="Wada">Teiji Wada</name><affiliation><inist:fA14 i1="01"><s1>MBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences</s1><s2>Vienna 1030</s2><s3>AUT</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Leong Poi, Howard" sort="Leong Poi, Howard" uniqKey="Leong Poi H" first="Howard" last="Leong-Poi">Howard Leong-Poi</name><affiliation><inist:fA14 i1="03"><s1>Department of Cardiology, St. Michael's Hospital</s1><s2>Toronto, Ontario MSB 1W8</s2><s3>CAN</s3><sZ>10 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Crackower, Michael A" sort="Crackower, Michael A" uniqKey="Crackower M" first="Michael A." last="Crackower">Michael A. Crackower</name><affiliation><inist:fA14 i1="04"><s1>Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research</s1><s2>Montreal, Quebec H3R 4P8</s2><s3>CAN</s3><sZ>11 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Fukamizu, Akiyoshi" sort="Fukamizu, Akiyoshi" uniqKey="Fukamizu A" first="Akiyoshi" last="Fukamizu">Akiyoshi Fukamizu</name><affiliation><inist:fA14 i1="05"><s1>Center for Tsukuba Advanced Research Alliance, University of Tsukuba</s1><s2>Tsukuba 305-8577</s2><s3>JPN</s3><sZ>12 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hui, Chi Chung" sort="Hui, Chi Chung" uniqKey="Hui C" first="Chi-Chung" last="Hui">Chi-Chung Hui</name><affiliation><inist:fA14 i1="06"><s1>Program in Developmental Biology, The Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto</s1><s2>Toronto, Ontario MG5 1X8</s2><s3>CAN</s3><sZ>13 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Hein, Lutz" sort="Hein, Lutz" uniqKey="Hein L" first="Lutz" last="Hein">Lutz Hein</name><affiliation><inist:fA14 i1="07"><s1>Department of Pharmacology, University of Freiburg</s1><s2>Freiburg 79104</s2><s3>DEU</s3><sZ>14 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Uhlig, Stefan" sort="Uhlig, Stefan" uniqKey="Uhlig S" first="Stefan" last="Uhlig">Stefan Uhlig</name><affiliation><inist:fA14 i1="08"><s1>Division of Pulmonary Pharmacology, Research Center Borstel</s1><s2>Borstel 23845</s2><s3>DEU</s3><sZ>15 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Slutsky, Arthur S" sort="Slutsky, Arthur S" uniqKey="Slutsky A" first="Arthur S." last="Slutsky">Arthur S. Slutsky</name><affiliation><inist: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></inist:fA14></affiliation></author><author><name sortKey="Chengyu Jiang" sort="Chengyu Jiang" uniqKey="Chengyu Jiang" last="Chengyu Jiang">CHENGYU JIANG</name><affiliation><inist:fA14 i1="02"><s1>National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College</s1><s2>Beijing 100005</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ></inist:fA14></affiliation></author><author><name sortKey="Penninger, Josef M" sort="Penninger, Josef M" uniqKey="Penninger J" first="Josef M." last="Penninger">Josef M. Penninger</name><affiliation><inist:fA14 i1="01"><s1>MBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences</s1><s2>Vienna 1030</s2><s3>AUT</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>18 aut.</sZ></inist:fA14></affiliation></author></analytic><series><title level="j" type="main">Nature : (London)</title><title level="j" type="abbreviated">Nature : (Lond.)</title><idno type="ISSN">0028-0836</idno><imprint><date when="2005">2005</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Nature : (London)</title><title level="j" type="abbreviated">Nature : (Lond.)</title><idno type="ISSN">0028-0836</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>ACE inhibitor</term><term>Animal</term><term>Chemotherapy</term><term>Etiology</term><term>Human</term><term>Mouse</term><term>Peptidyl-dipeptidase A</term><term>Recombinant protein</term><term>Respiratory distress</term><term>Severe acute respiratory syndrome</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Syndrome respiratoire aigu sévère</term><term>Homme</term><term>Détresse respiratoire</term><term>Etiologie</term><term>Peptidyl-dipeptidase A</term><term>Inhibiteur angiotensin converting enzyme</term><term>Animal</term><term>Souris</term><term>Protéine recombinante</term><term>Chimiothérapie</term><term>ACE2</term></keywords></textClass></profileDesc></teiHeader><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></TEI><inist><standard h6="B"><pA><fA01 i1="01" i2="1"><s0>0028-0836</s0></fA01><fA02 i1="01"><s0>NATUAS</s0></fA02><fA03 i2="1"><s0>Nature : (Lond.)</s0></fA03><fA05><s2>436</s2></fA05><fA06><s2>7047</s2></fA06><fA08 i1="01" i2="1" l="ENG"><s1>Angiotensin-converting enzyme 2 protects from severe acute lung failure</s1></fA08><fA11 i1="01" i2="1"><s1>IMAI (Yumiko)</s1></fA11><fA11 i1="02" i2="1"><s1>KUBA (Keiji)</s1></fA11><fA11 i1="03" i2="1"><s1>SHUAN RAO</s1></fA11><fA11 i1="04" i2="1"><s1>YI HUAN</s1></fA11><fA11 i1="05" i2="1"><s1>FENG GUO</s1></fA11><fA11 i1="06" i2="1"><s1>BIN GUAN</s1></fA11><fA11 i1="07" i2="1"><s1>PENG YANG</s1></fA11><fA11 i1="08" i2="1"><s1>SARAO (Renu)</s1></fA11><fA11 i1="09" i2="1"><s1>WADA (Teiji)</s1></fA11><fA11 i1="10" i2="1"><s1>LEONG-POI (Howard)</s1></fA11><fA11 i1="11" i2="1"><s1>CRACKOWER (Michael A.)</s1></fA11><fA11 i1="12" i2="1"><s1>FUKAMIZU (Akiyoshi)</s1></fA11><fA11 i1="13" i2="1"><s1>HUI (Chi-Chung)</s1></fA11><fA11 i1="14" i2="1"><s1>HEIN (Lutz)</s1></fA11><fA11 i1="15" i2="1"><s1>UHLIG (Stefan)</s1></fA11><fA11 i1="16" i2="1"><s1>SLUTSKY (Arthur S.)</s1></fA11><fA11 i1="17" i2="1"><s1>CHENGYU JIANG</s1></fA11><fA11 i1="18" i2="1"><s1>PENNINGER (Josef M.)</s1></fA11><fA14 i1="01"><s1>MBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences</s1><s2>Vienna 1030</s2><s3>AUT</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>8 aut.</sZ><sZ>9 aut.</sZ><sZ>18 aut.</sZ></fA14><fA14 i1="02"><s1>National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & Peking Union Medical College</s1><s2>Beijing 100005</s2><s3>CHN</s3><sZ>3 aut.</sZ><sZ>4 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>7 aut.</sZ><sZ>17 aut.</sZ></fA14><fA14 i1="03"><s1>Department of Cardiology, St. Michael's Hospital</s1><s2>Toronto, Ontario MSB 1W8</s2><s3>CAN</s3><sZ>10 aut.</sZ></fA14><fA14 i1="04"><s1>Department of Biochemistry and Molecular Biology, Merck Frosst Centre for Therapeutic Research</s1><s2>Montreal, Quebec H3R 4P8</s2><s3>CAN</s3><sZ>11 aut.</sZ></fA14><fA14 i1="05"><s1>Center for Tsukuba Advanced Research Alliance, University of Tsukuba</s1><s2>Tsukuba 305-8577</s2><s3>JPN</s3><sZ>12 aut.</sZ></fA14><fA14 i1="06"><s1>Program in Developmental Biology, The Hospital for Sick Children and Department of Molecular and Medical Genetics, University of Toronto</s1><s2>Toronto, Ontario MG5 1X8</s2><s3>CAN</s3><sZ>13 aut.</sZ></fA14><fA14 i1="07"><s1>Department of Pharmacology, University of Freiburg</s1><s2>Freiburg 79104</s2><s3>DEU</s3><sZ>14 aut.</sZ></fA14><fA14 i1="08"><s1>Division of Pulmonary Pharmacology, Research Center Borstel</s1><s2>Borstel 23845</s2><s3>DEU</s3><sZ>15 aut.</sZ></fA14><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></fA14><fA20><s1>112-116</s1></fA20><fA21><s1>2005</s1></fA21><fA23 i1="01"><s0>ENG</s0></fA23><fA43 i1="01"><s1>INIST</s1><s2>142</s2><s5>354000138281660220</s5></fA43><fA44><s0>0000</s0><s1>© 2005 INIST-CNRS. All rights reserved.</s1></fA44><fA45><s0>30 ref.</s0></fA45><fA47 i1="01" i2="1"><s0>05-0401946</s0></fA47><fA60><s1>P</s1><s3>CR</s3></fA60><fA61><s0>A</s0></fA61><fA64 i1="01" i2="1"><s0>Nature : (London)</s0></fA64><fA66 i1="01"><s0>GBR</s0></fA66><fC01 i1="01" l="ENG"><s0>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.</s0></fC01><fC02 i1="01" i2="X"><s0>002B05C02C</s0></fC02><fC03 i1="01" i2="X" l="FRE"><s0>Syndrome respiratoire aigu sévère</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="01" i2="X" l="ENG"><s0>Severe acute respiratory syndrome</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="01" i2="X" l="SPA"><s0>Síndrome respiratorio agudo severo</s0><s2>NM</s2><s5>02</s5></fC03><fC03 i1="02" i2="X" l="FRE"><s0>Homme</s0><s5>03</s5></fC03><fC03 i1="02" i2="X" l="ENG"><s0>Human</s0><s5>03</s5></fC03><fC03 i1="02" i2="X" l="SPA"><s0>Hombre</s0><s5>03</s5></fC03><fC03 i1="03" i2="X" l="FRE"><s0>Détresse respiratoire</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="ENG"><s0>Respiratory distress</s0><s5>05</s5></fC03><fC03 i1="03" i2="X" l="SPA"><s0>Trastorno respiratorio</s0><s5>05</s5></fC03><fC03 i1="04" i2="X" l="FRE"><s0>Etiologie</s0><s5>06</s5></fC03><fC03 i1="04" i2="X" l="ENG"><s0>Etiology</s0><s5>06</s5></fC03><fC03 i1="04" i2="X" l="SPA"><s0>Etiología</s0><s5>06</s5></fC03><fC03 i1="05" i2="X" l="FRE"><s0>Peptidyl-dipeptidase A</s0><s2>FE</s2><s5>08</s5></fC03><fC03 i1="05" i2="X" l="ENG"><s0>Peptidyl-dipeptidase A</s0><s2>FE</s2><s5>08</s5></fC03><fC03 i1="05" i2="X" l="SPA"><s0>Peptidyl-dipeptidase A</s0><s2>FE</s2><s5>08</s5></fC03><fC03 i1="06" i2="X" l="FRE"><s0>Inhibiteur angiotensin converting enzyme</s0><s5>09</s5></fC03><fC03 i1="06" i2="X" l="ENG"><s0>ACE inhibitor</s0><s5>09</s5></fC03><fC03 i1="06" i2="X" l="SPA"><s0>Inhibidor angiotensin converting enzyme</s0><s5>09</s5></fC03><fC03 i1="07" i2="X" l="FRE"><s0>Animal</s0><s5>11</s5></fC03><fC03 i1="07" i2="X" l="ENG"><s0>Animal</s0><s5>11</s5></fC03><fC03 i1="07" i2="X" l="SPA"><s0>Animal</s0><s5>11</s5></fC03><fC03 i1="08" i2="X" l="FRE"><s0>Souris</s0><s5>12</s5></fC03><fC03 i1="08" i2="X" l="ENG"><s0>Mouse</s0><s5>12</s5></fC03><fC03 i1="08" i2="X" l="SPA"><s0>Ratón</s0><s5>12</s5></fC03><fC03 i1="09" i2="X" l="FRE"><s0>Protéine recombinante</s0><s5>14</s5></fC03><fC03 i1="09" i2="X" l="ENG"><s0>Recombinant protein</s0><s5>14</s5></fC03><fC03 i1="09" i2="X" l="SPA"><s0>Proteína recombinante</s0><s5>14</s5></fC03><fC03 i1="10" i2="X" l="FRE"><s0>Chimiothérapie</s0><s5>15</s5></fC03><fC03 i1="10" i2="X" l="ENG"><s0>Chemotherapy</s0><s5>15</s5></fC03><fC03 i1="10" i2="X" l="SPA"><s0>Quimioterapia</s0><s5>15</s5></fC03><fC03 i1="11" i2="X" l="FRE"><s0>ACE2</s0><s4>INC</s4><s5>86</s5></fC03><fC07 i1="01" i2="X" l="FRE"><s0>Virose</s0></fC07><fC07 i1="01" i2="X" l="ENG"><s0>Viral disease</s0></fC07><fC07 i1="01" i2="X" l="SPA"><s0>Virosis</s0></fC07><fC07 i1="02" i2="X" l="FRE"><s0>Infection</s0></fC07><fC07 i1="02" i2="X" l="ENG"><s0>Infection</s0></fC07><fC07 i1="02" i2="X" l="SPA"><s0>Infección</s0></fC07><fC07 i1="03" i2="X" l="FRE"><s0>Peptidyl-dipeptidases</s0><s2>FE</s2></fC07><fC07 i1="03" i2="X" l="ENG"><s0>Peptidyl-dipeptidases</s0><s2>FE</s2></fC07><fC07 i1="03" i2="X" l="SPA"><s0>Peptidyl-dipeptidases</s0><s2>FE</s2></fC07><fC07 i1="04" i2="X" l="FRE"><s0>Peptidases</s0><s2>FE</s2></fC07><fC07 i1="04" i2="X" l="ENG"><s0>Peptidases</s0><s2>FE</s2></fC07><fC07 i1="04" i2="X" l="SPA"><s0>Peptidases</s0><s2>FE</s2></fC07><fC07 i1="05" i2="X" l="FRE"><s0>Hydrolases</s0><s2>FE</s2></fC07><fC07 i1="05" i2="X" l="ENG"><s0>Hydrolases</s0><s2>FE</s2></fC07><fC07 i1="05" i2="X" l="SPA"><s0>Hydrolases</s0><s2>FE</s2></fC07><fC07 i1="06" i2="X" l="FRE"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="06" i2="X" l="ENG"><s0>Enzyme</s0><s2>FE</s2></fC07><fC07 i1="06" i2="X" l="SPA"><s0>Enzima</s0><s2>FE</s2></fC07><fC07 i1="07" i2="X" l="FRE"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="07" i2="X" l="ENG"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="07" i2="X" l="SPA"><s0>Rodentia</s0><s2>NS</s2></fC07><fC07 i1="08" i2="X" l="FRE"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="08" i2="X" l="ENG"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="08" i2="X" l="SPA"><s0>Mammalia</s0><s2>NS</s2></fC07><fC07 i1="09" i2="X" l="FRE"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="09" i2="X" l="ENG"><s0>Vertebrata</s0><s2>NS</s2></fC07><fC07 i1="09" i2="X" l="SPA"><s0>Vertebrata</s0><s2>NS</s2></fC07><fN21><s1>283</s1></fN21></pA></standard><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><LO>INIST-142.354000138281660220</LO><ID>05-0401946</ID></server></inist></record>Pour manipuler ce document sous Unix (Dilib)
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