Angiotensin-converting enzyme 2 protects from severe acute lung failure
Identifieur interne : 005228 ( Main/Merge ); précédent : 005227; suivant : 005229Angiotensin-converting enzyme 2 protects from severe acute lung failure
Auteurs : Yumiko Imai [Autriche] ; Keiji Kuba [Autriche] ; SHUAN RAO [République populaire de Chine] ; YI HUAN [République populaire de Chine] ; FENG GUO [République populaire de Chine] ; BIN GUAN [République populaire de Chine] ; PENG YANG [République populaire de Chine] ; Renu Sarao [Autriche] ; Teiji Wada [Autriche] ; Howard Leong-Poi [Canada] ; Michael A. Crackower [Canada] ; Akiyoshi Fukamizu [Japon] ; Chi-Chung Hui [Canada] ; Lutz Hein [Allemagne] ; Stefan Uhlig [Allemagne] ; Arthur S. Slutsky [Canada] ; CHENGYU JIANG [République populaire de Chine] ; Josef M. Penninger [Autriche]Source :
- Nature : (London) [ 0028-0836 ] ; 2005.
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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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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><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Shuan Rao" sort="Shuan Rao" uniqKey="Shuan Rao" last="Shuan Rao">SHUAN RAO</name><affiliation wicri:level="1"><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><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Yi Huan" sort="Yi Huan" uniqKey="Yi Huan" last="Yi Huan">YI HUAN</name><affiliation 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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><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></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 wicri:level="1"><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><country>Canada</country><wicri:noRegion>Toronto, Ontario MSB 1W8</wicri:noRegion></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 wicri:level="1"><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><country>Canada</country><wicri:noRegion>Montreal, Quebec H3R 4P8</wicri:noRegion></affiliation></author><author><name sortKey="Fukamizu, Akiyoshi" sort="Fukamizu, Akiyoshi" uniqKey="Fukamizu A" first="Akiyoshi" last="Fukamizu">Akiyoshi Fukamizu</name><affiliation wicri:level="1"><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><country>Japon</country><wicri:noRegion>Tsukuba 305-8577</wicri:noRegion></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 wicri:level="4"><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><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Hein, Lutz" sort="Hein, Lutz" uniqKey="Hein L" first="Lutz" last="Hein">Lutz Hein</name><affiliation wicri:level="3"><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><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Uhlig, Stefan" sort="Uhlig, Stefan" uniqKey="Uhlig S" first="Stefan" last="Uhlig">Stefan Uhlig</name><affiliation wicri:level="1"><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><country>Allemagne</country><wicri:noRegion>23845</wicri:noRegion><wicri:noRegion>Research Center Borstel</wicri:noRegion><wicri:noRegion>Borstel 23845</wicri:noRegion></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 wicri:level="4"><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><country>Canada</country><wicri:noRegion>Toronto, Ontario MSB 1W8</wicri:noRegion><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Chengyu Jiang" sort="Chengyu Jiang" uniqKey="Chengyu Jiang" last="Chengyu Jiang">CHENGYU JIANG</name><affiliation wicri:level="1"><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><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></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 wicri:level="1"><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><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></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><idno type="wicri:Area/PascalFrancis/Curation">000376</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000708</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000708</idno><idno type="wicri:doubleKey">0028-0836:2005:Imai Y:angiotensin:converting:enzyme</idno><idno type="wicri:Area/Main/Merge">005228</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 wicri:level="1"><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><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Kuba, Keiji" sort="Kuba, Keiji" uniqKey="Kuba K" first="Keiji" last="Kuba">Keiji Kuba</name><affiliation wicri:level="1"><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><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Shuan Rao" sort="Shuan Rao" uniqKey="Shuan Rao" last="Shuan Rao">SHUAN RAO</name><affiliation wicri:level="1"><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><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Yi Huan" sort="Yi Huan" uniqKey="Yi Huan" last="Yi Huan">YI HUAN</name><affiliation wicri:level="1"><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><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Feng Guo" sort="Feng Guo" uniqKey="Feng Guo" last="Feng Guo">FENG GUO</name><affiliation wicri:level="1"><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><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Bin Guan" sort="Bin Guan" uniqKey="Bin Guan" last="Bin Guan">BIN GUAN</name><affiliation wicri:level="1"><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><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Peng Yang" sort="Peng Yang" uniqKey="Peng Yang" last="Peng Yang">PENG YANG</name><affiliation wicri:level="1"><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><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></affiliation></author><author><name sortKey="Sarao, Renu" sort="Sarao, Renu" uniqKey="Sarao R" first="Renu" last="Sarao">Renu Sarao</name><affiliation wicri:level="1"><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><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></affiliation></author><author><name sortKey="Wada, Teiji" sort="Wada, Teiji" uniqKey="Wada T" first="Teiji" last="Wada">Teiji Wada</name><affiliation wicri:level="1"><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><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></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 wicri:level="1"><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><country>Canada</country><wicri:noRegion>Toronto, Ontario MSB 1W8</wicri:noRegion></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 wicri:level="1"><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><country>Canada</country><wicri:noRegion>Montreal, Quebec H3R 4P8</wicri:noRegion></affiliation></author><author><name sortKey="Fukamizu, Akiyoshi" sort="Fukamizu, Akiyoshi" uniqKey="Fukamizu A" first="Akiyoshi" last="Fukamizu">Akiyoshi Fukamizu</name><affiliation wicri:level="1"><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><country>Japon</country><wicri:noRegion>Tsukuba 305-8577</wicri:noRegion></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 wicri:level="4"><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><country>Canada</country><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName><orgName type="university">Université de Toronto</orgName></affiliation></author><author><name sortKey="Hein, Lutz" sort="Hein, Lutz" uniqKey="Hein L" first="Lutz" last="Hein">Lutz Hein</name><affiliation wicri:level="3"><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><country>Allemagne</country><placeName><region type="land" nuts="1">Bade-Wurtemberg</region><region type="district" nuts="2">District de Fribourg-en-Brisgau</region><settlement type="city">Fribourg-en-Brisgau</settlement></placeName></affiliation></author><author><name sortKey="Uhlig, Stefan" sort="Uhlig, Stefan" uniqKey="Uhlig S" first="Stefan" last="Uhlig">Stefan Uhlig</name><affiliation wicri:level="1"><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><country>Allemagne</country><wicri:noRegion>23845</wicri:noRegion><wicri:noRegion>Research Center Borstel</wicri:noRegion><wicri:noRegion>Borstel 23845</wicri:noRegion></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 wicri:level="4"><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><country>Canada</country><wicri:noRegion>Toronto, Ontario MSB 1W8</wicri:noRegion><orgName type="university">Université de Toronto</orgName><placeName><settlement type="city">Toronto</settlement><region type="state">Ontario</region></placeName></affiliation></author><author><name sortKey="Chengyu Jiang" sort="Chengyu Jiang" uniqKey="Chengyu Jiang" last="Chengyu Jiang">CHENGYU JIANG</name><affiliation wicri:level="1"><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><country>République populaire de Chine</country><placeName><settlement type="city">Pékin</settlement></placeName></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 wicri:level="1"><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><country>Autriche</country><placeName><settlement type="city">Vienne (Autriche)</settlement><region nuts="2" type="province">Vienne (Autriche)</region></placeName></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><keywords scheme="Wicri" type="topic" xml:lang="fr"><term>Homme</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><affiliations><list><country><li>Allemagne</li><li>Autriche</li><li>Canada</li><li>Japon</li><li>République populaire de Chine</li></country><region><li>Bade-Wurtemberg</li><li>District de Fribourg-en-Brisgau</li><li>Ontario</li><li>Vienne (Autriche)</li></region><settlement><li>Fribourg-en-Brisgau</li><li>Pékin</li><li>Toronto</li><li>Vienne (Autriche)</li></settlement><orgName><li>Université de Toronto</li></orgName></list><tree><country name="Autriche"><region name="Vienne (Autriche)"><name sortKey="Imai, Yumiko" sort="Imai, Yumiko" uniqKey="Imai Y" first="Yumiko" last="Imai">Yumiko Imai</name></region><name sortKey="Kuba, Keiji" sort="Kuba, Keiji" uniqKey="Kuba K" first="Keiji" last="Kuba">Keiji Kuba</name><name sortKey="Penninger, Josef M" sort="Penninger, Josef M" uniqKey="Penninger J" first="Josef M." last="Penninger">Josef M. Penninger</name><name sortKey="Sarao, Renu" sort="Sarao, Renu" uniqKey="Sarao R" first="Renu" last="Sarao">Renu Sarao</name><name sortKey="Wada, Teiji" sort="Wada, Teiji" uniqKey="Wada T" first="Teiji" last="Wada">Teiji Wada</name></country><country name="République populaire de Chine"><noRegion><name sortKey="Shuan Rao" sort="Shuan Rao" uniqKey="Shuan Rao" last="Shuan Rao">SHUAN RAO</name></noRegion><name sortKey="Bin Guan" sort="Bin Guan" uniqKey="Bin Guan" last="Bin Guan">BIN GUAN</name><name sortKey="Chengyu Jiang" sort="Chengyu Jiang" uniqKey="Chengyu Jiang" last="Chengyu Jiang">CHENGYU JIANG</name><name sortKey="Feng Guo" sort="Feng Guo" uniqKey="Feng Guo" last="Feng Guo">FENG GUO</name><name sortKey="Peng Yang" sort="Peng Yang" uniqKey="Peng Yang" last="Peng Yang">PENG YANG</name><name sortKey="Yi Huan" sort="Yi Huan" uniqKey="Yi Huan" last="Yi Huan">YI HUAN</name></country><country name="Canada"><noRegion><name sortKey="Leong Poi, Howard" sort="Leong Poi, Howard" uniqKey="Leong Poi H" first="Howard" last="Leong-Poi">Howard Leong-Poi</name></noRegion><name sortKey="Crackower, Michael A" sort="Crackower, Michael A" uniqKey="Crackower M" first="Michael A." last="Crackower">Michael A. Crackower</name><name sortKey="Hui, Chi Chung" sort="Hui, Chi Chung" uniqKey="Hui C" first="Chi-Chung" last="Hui">Chi-Chung Hui</name><name sortKey="Slutsky, Arthur S" sort="Slutsky, Arthur S" uniqKey="Slutsky A" first="Arthur S." last="Slutsky">Arthur S. Slutsky</name></country><country name="Japon"><noRegion><name sortKey="Fukamizu, Akiyoshi" sort="Fukamizu, Akiyoshi" uniqKey="Fukamizu A" first="Akiyoshi" last="Fukamizu">Akiyoshi Fukamizu</name></noRegion></country><country name="Allemagne"><region name="Bade-Wurtemberg"><name sortKey="Hein, Lutz" sort="Hein, Lutz" uniqKey="Hein L" first="Lutz" last="Hein">Lutz Hein</name></region><name sortKey="Uhlig, Stefan" sort="Uhlig, Stefan" uniqKey="Uhlig S" first="Stefan" last="Uhlig">Stefan Uhlig</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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