Jump to ContentJump to Main Navigation
Show Summary Details
More options …

Clinical Chemistry and Laboratory Medicine (CCLM)

Published in Association with the European Federation of Clinical Chemistry and Laboratory Medicine (EFLM)

Editor-in-Chief: Plebani, Mario

Ed. by Gillery, Philippe / Greaves, Ronda / Lackner, Karl J. / Lippi, Giuseppe / Melichar, Bohuslav / Payne, Deborah A. / Schlattmann, Peter

IMPACT FACTOR 2017: 3.556

CiteScore 2017: 2.34

SCImago Journal Rank (SJR) 2017: 1.114
Source Normalized Impact per Paper (SNIP) 2017: 1.188

See all formats and pricing
More options …
Volume 40, Issue 3


New Aspects on Angiotensin-Converting Enzyme: from Gene to Disease

Bruno Baudin
Published Online: 2005-06-01 | DOI: https://doi.org/10.1515/CCLM.2002.042


Angiotensin-converting enzyme (ACE) is a well known zinc-metallopeptidase that converts angiotensin I to the potent vasoconstrictor angiotensin II and that degrades bradykinin, a powerful vasodilator, both for regulation of vascular tone and cardiac functions. Other natural substrates of ACE were identified broadening the functions of this enzyme within different physiological contexts such as neuronal metabolism, hematopoiesis, digestion and reproduction. Synthetic substrates were developed for the determination of ACE activity in various biological fluids, mostly human plasma, for the diagnosis of sarcoidosis and other granulomatous diseases. After the successful use of captopril, the first ACE inhibitor in the treatment of hypertension, a number of molecules were synthesized and used in the treatment of congestive heart failure and for preventing cardiac impairment after myocardial infarction. This class of antihypertensive drugs benefited from structural data on carboxypeptidases active site, as ACE molecule has not yet been crystallized. In the last two decades ACE gene has been cloned that allowed the identification (i) of two isoenzymes, one called somatic ACE resulting from gene duplication and primarily expressed in endothelial cells, and the other, called germinative or testicular ACE, resulting from the transcription in the male reproductive system of a more simple gene, (ii) of an hydrophobic C-terminal peptide for membrane-anchoring and specifically cleaved by a metalloprotease to release soluble forms of both isoenzymes, and (iii) of several allelic polymorphisms, one of them consisting of an insertion/deletion (I/D) polymorphism in a short intronic Alu sequence that could account for half the variance in plasma ACE level and resulting in a large inter- individual variability; moreover this I/D polymorphism was proposed as a genetic marker for identifying individuals at high risk of ischemic heart disease and of anticipating in one individual the efficacy of the antihypertensive therapy, although conflicting data arose from the past decade literature. Moreover, ACE gene cloning has confirmed the expression of the enzyme in endothelial cell, in particular as an ecto-enzyme facing the vascular lumen, but not to the same extent with regard to the vascular origin of the cells. Plasma ACE in healthy subjects arises essentially from the endothelium. On the other hand, in granulomatous diseases where a local stimulation of macrophages leads to an abnormal ACE secretion, it can also be found in other biological fluids such as cerebrospinal and broncho-alveolar fluids. Low plasma ACE levels result from endothelium impairment such as in deep vein thrombosis or in endothelio-toxic anticancer therapies. Another cause of low, sometimes undetectable, plasma ACE levels is the use of an ACE inhibitor, but this is without any significance with regard to its clinical benefits. Albeit molecular cloning has provided a number of new details on ACE structure and function, many questions still remain, in particular about its tertiary structure including glycosylations, about its tissue-specific expression and regulation, and also about the exact significance of the I/D polymorphism in cardiovascular pathology including the pharmacogenomic field.

About the article

Published Online: 2005-06-01

Published in Print: 2002-04-10

Citation Information: Clinical Chemistry and Laboratory Medicine, Volume 40, Issue 3, Pages 256–265, ISSN (Print) 1434-6621, DOI: https://doi.org/10.1515/CCLM.2002.042.

Export Citation

Citing Articles

Here you can find all Crossref-listed publications in which this article is cited. If you would like to receive automatic email messages as soon as this article is cited in other publications, simply activate the “Citation Alert” on the top of this page.

Hamdouni Haithem, Achour Ons, Naija Salma, Rejeb Jihène, Aounallah Mariam, Mhiri Mariem, Noureddine Mariem, Ben Rejeb Nabila, Omezzine Asma, Ben Amor Sana, Benammou Sofien, and Bouslama Ali
International Journal of Neuroscience, 2017, Page 1
Viroj Wiwanitkit
Clinical and Applied Thrombosis/Hemostasis, 2004, Volume 10, Number 2, Page 179
Hongli He, Ling Liu, Qihong Chen, Airan Liu, Shixia Cai, Yi Yang, Xiaomin Lu, and Haibo Qiu
Cell Transplantation, 2015, Volume 24, Number 9, Page 1699
Pan Liu, Jan Wysocki, Peter Serfozo, Minghao Ye, Tomokazu Souma, Daniel Batlle, and Jing Jin
Scientific Reports, 2017, Volume 7, Page 45473
Sinda Mahjoub, Sounira Mehri, Rafik Bousaada, Fatma Ouarda, Amira Zaroui, Bechir Zouari, Rachid Mechmeche, Mohamed Hammami, and Saida Ben Arab
Journal of the Renin-Angiotensin-Aldosterone System, 2010, Volume 11, Number 3, Page 187
AO Conrady, IO Kiselev, NI Usachev, AN Krutikov, OI Yakovleva, EV Polunicheva, OA Ovchinnikova, and AV Panov
Journal of International Medical Research, 2005, Volume 33, Number 1_suppl, Page 30A
Wei Nie, Yuansheng Zang, Jiquan Chen, Tao Liu, Lin Xiao, and Qingyu Xiu
Journal of the Renin-Angiotensin-Aldosterone System, 2014, Volume 15, Number 4, Page 585
Natasha A. Hamilton, Imke Tammen, Herman W. Raadsma, and Vincent Laudet
PLoS ONE, 2013, Volume 8, Number 2, Page e55434
Lydia Michelke, Andreas Deussen, Peter Dieterich, and Melanie Martin
Journal of Functional Foods, 2017, Volume 28, Page 299
Abdelkader Chalghoum, Yosri Noichri, Azza Dandana, Bruno Baudin, Abdelhédi Miled, and Salima Ferchichi
BMC Cardiovascular Disorders, 2016, Volume 16, Number 1
Kshetrimayum Birla Singh
Journal of Biosciences and Medicines, 2016, Volume 04, Number 07, Page 12
Geoffrey Masuyer, Christopher J. Yates, Edward D. Sturrock, and K. Ravi Acharya
Biological Chemistry, 2014, Volume 395, Number 10
Hong Wang, Kun Zhang, Haifeng Qin, Lin Yang, Liyu Zhang, and Yanyan Cao
Medicine, 2015, Volume 94, Number 30, Page e883
Xiaofang Zhang and Fangzhu Liu
Clinical and Experimental Medicine, 2016, Volume 16, Number 3, Page 423
Marília Dourado, Joana Bento, Luís Mesquita, Alcide Marques, Sofia Vale-Pereira, Ana Bela Sarmento Ribeiro, and Anabela Mota Pinto
Revista Portuguesa de Pneumologia, 2005, Volume 11, Number 2, Page 111
Valentina Ginevičienė, Erinija Pranckevičienė, Kazys Milašius, and Vaidutis Kučinskas
Acta medica Lituanica, 2010, Volume 17, Number 1, Page 1
Offer Amir, Ruthie Amir, Chen Yamin, Eric Attias, Nir Eynon, Moran Sagiv, Michael Sagiv, and Yoav Meckel
Experimental Physiology, 2007, Volume 92, Number 5, Page 881
Antonella Borrelli, Antonietta Schiattarella, Patrizia Bonelli, Franca Maria Tuccillo, Franco Maria Buonaguro, and Aldo Mancini
BioMed Research International, 2014, Volume 2014, Page 1
Balázs Liktor, Péter Csomor, Csaba Sándor Szász, István Sziklai, and Tamás Karosi
Otology & Neurotology, 2013, Volume 34, Number 5, Page 808
Frank Stüber
American Journal of Respiratory and Critical Care Medicine, 2002, Volume 166, Number 5, Page 633
Soha Namazi, Ahmad Monabati, Shirin Ardeshir-Rouhani-Fard, and Negar Azarpira
Tumor Biology, 2013, Volume 34, Number 5, Page 2899
A.S. Thomas, A.B. Mehta, and D.A. Hughes
Blood Cells, Molecules, and Diseases, 2013, Volume 50, Number 3, Page 212
A. Chalghoum, Y. Noichri, A. Dandana, I. Gammoudi, S. Khelil, S. Ferchichi, and A. Miled
Immuno-analyse & Biologie Spécialisée, 2012, Volume 27, Number 5, Page 244
Hadassa M. Jochemsen, Mirjam I. Geerlings, Frank L. Visseren, Ale Algra, Yolanda van der Graaf, and Majon Muller
Atherosclerosis, 2012, Volume 224, Number 2, Page 486
José M. Matés, Juan A. Segura, Francisco J. Alonso, and Javier Márquez
Archives of Toxicology, 2012, Volume 86, Number 11, Page 1649
Amal M.H. Mackawy, Mohammed E.H. Badawy, and Ola Abd El-Rahman Yossef Megahed
Egyptian Journal of Medical Human Genetics, 2012, Volume 13, Number 3, Page 291
S. Nadya J. Kazzi and Michael W. Quasney
The Journal of Pediatrics, 2005, Volume 147, Number 6, Page 818
Adel A. Zalata, Heba K. Morsy, Abd El-Naser Badawy, Samir Elhanbly, and Taymour Mostafa
The Journal of Urology, 2012, Volume 187, Number 5, Page 1776
Sayed Mohammad Shafiee, Mohsen Firoozrai, Saeedeh Salimi, Hamid Zand, Behnoosh Hesabi, and Ahmad Mohebbi
Pathophysiology, 2010, Volume 17, Number 3, Page 163
B. Baudin, B. Bénéteau-Burnat, and M. Vaubourdolle
Immuno-analyse & Biologie Spécialisée, 2005, Volume 20, Number 3, Page 161
A. Chalghoum, Y. Noichri, Z. Jaidane, I. Gammoudi, H. Chahed, A. Dandana, S. Khelil, L. Chkioua, Y. Chaabouni, G. Jeridi, S. Ferchichi, and A. Miled
Immuno-analyse & Biologie Spécialisée, 2010, Volume 25, Number 4, Page 185
D. Seripa, M. Franceschi, M. G. Matera, F. Panza, P. G. Kehoe, C. Gravina, G. Orsitto, V. Solfrizzi, G. Di Minno, B. Dallapiccola, and A. Pilotto
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences, 2006, Volume 61, Number 9, Page 918
Roelie M Wösten-van Asperen, René Lutter, Patricia A Specht, Gert N Moll, Job B van Woensel, Chris M van der Loos, Harry van Goor, Jelena Kamilic, Sandrine Florquin, and Albert P Bos
The Journal of Pathology, 2011, Volume 225, Number 4, Page 618
A. Chalghoum, Y. Noichri, L. Chkioua, I. Gammoudi, A. Dandana, H. Chahed, S. Khelil, G. Jeridi, B. Baudin, S. Ferchichi, and A. Miled
Annales de Cardiologie et d'Angéiologie, 2011, Volume 60, Number 3, Page 135
J.Antonio Casal, Alfredo Robles, and J.Carlos Tutor
Clinical Biochemistry, 2003, Volume 36, Number 7, Page 553
Sounira Mehri, Nadia Koubaa, Amel Nakbi, Sonia Hammami, Raja Chaaba, Sinda Mahjoub, Bechir Zouari, Mohamed Abid, Saida Ben Arab, Bruno Baudin, and Mohamed Hammami
Clinical Biochemistry, 2010, Volume 43, Number 3, Page 259
N Macours, K Hens, C Francis, A De Loof, and R Huybrechts
Journal of Insect Physiology, 2003, Volume 49, Number 8, Page 739
P. Dahlem, W.M.C. van Aalderen, and A.P. Bos
Paediatric Respiratory Reviews, 2007, Volume 8, Number 4, Page 348
Chafic Karam and Salam Koussa
Journal of Clinical Neuroscience, 2008, Volume 15, Number 11, Page 1274
Samira Roufik, Sylvie F. Gauthier, and Sylvie L. Turgeon
International Dairy Journal, 2007, Volume 17, Number 5, Page 471
Lilia C De Jesus, S Nadya J Kazzi, Mary K Dahmer, Xinguang Chen, and Michael W Quasney
Acta Paediatrica, 2011, Volume 100, Number 10, Page 1326
Sabine C.A. Meijvis, Marie Claire A. Cornips, Henrik Endeman, Henk J.T. Ruven, A.H. Jan Danser, Douwe H. Biesma, Hubert G.M. Leufkens, Willem Jan W. Bos, and Ewoudt M.W. van de Garde
Clinical Chemistry and Laboratory Medicine, 2011, Volume 49, Number 9
Satoru Itoyama, Naoto Keicho, Tran Quy, Nguyen Chi Phi, Hoang Thuy Long, Le Dang Ha, Vo Van Ban, Jun Ohashi, Minako Hijikata, Ikumi Matsushita, Akihiko Kawana, Hideki Yanai, Teruo Kirikae, Tadatoshi Kuratsuji, and Takehiko Sasazuki
Biochemical and Biophysical Research Communications, 2004, Volume 323, Number 3, Page 1124
Sounira Mehri, Nadia Koubaa, Sonia Hammami, Sinda Mahjoub, Raja Chaaba, Amel Nakbi, Bechir Zouari, Mohamed Abid, Saida Ben Arab, Bruno Baudin, and Mohamed Hammami
Life Sciences, 2010, Volume 87, Number 1-2, Page 49
A. Stavroulaki and G. Pramantiotis
Journal of the European Academy of Dermatology and Venereology, 2011, Volume 25, Number 9, Page 1116
Myosotis Massidda, Giuseppe Vona, and Carla M. Calò
European Journal of Sport Science, 2011, Volume 11, Number 3, Page 149
Annette M. Müller, Kai M. Gruhn, Martina C. Herwig, and Michael Tsokos
Legal Medicine, 2008, Volume 10, Number 5, Page 257
Alberto Pilotto, Maria G. Matera, Luigi Ferrucci, Daniele Sancarlo, Gioacchino Leandro, Grazia D'Onofrio, Davide Seripa, Filomena Addante, Marilisa Franceschi, and Bruno Dallapiccola
Rejuvenation Research, 2009, Volume 12, Number 4, Page 239
Sounira Mehri, Bruno Baudin, Sinda Mahjoub, Amira Zaroui, Bénédicte Bénéteau-Burnat, Rachid Mechmeche, Mohamed Hammami, and Saïda Ben Arab
Genetic Testing and Molecular Biomarkers, 2010, Volume 14, Number 1, Page 85
Valentina Ginevičienė, Erinija Pranckevičienė, Kazys Milašius, and Vaidutis Kučinskas
Open Life Sciences, 2011, Volume 6, Number 1
Soha Namazi, Ahmad Monabati, Shirin Ardeshir-Rouhani-Fard, and Negar Azarpira
Molecular Carcinogenesis, 2010, Volume 49, Number 12, Page 1022
Nevin Oruc, Georgios I. Papachristou, Haritha Avula, Adam Slivka, Janette Lamb, and David C. Whitcomb
HPB, 2009, Volume 11, Number 1, Page 45
Laurence Deloffre, Pierre-Eric Sautiere, Roger Huybrechts, Korneel Hens, Didier Vieau, and Michel Salzet
European Journal of Biochemistry, 2004, Volume 271, Number 11, Page 2101
O Bespalova, T Ivashchenko, O Tarasenko, G Demin, E Ajlamazjan, and V Baranov
Balkan Journal of Medical Genetics, 2007, Volume 10, Number 1
Sylva L Schwager, Adriana K Carmona, and Edward D Sturrock
Nature Protocols, 2006, Volume 1, Number 4, Page 1961
Yusuke Watanabe, Tsutomu Inoue, Hirokazu Okada, Shuhei Kotaki, Yoshihiko Kanno, Tomohiro Kikuta, and Hiromichi Suzuki
Internal Medicine, 2006, Volume 45, Number 16, Page 947
Satish Kumar Taneja and Reshu Mandal
Biological Trace Element Research, 2007, Volume 120, Number 1-3, Page 61
Adrian Kruit, Jan C. Grutters, Henk J.T. Ruven, Hiroe Sato, Takateru Izumi, Sonoko Nagai, Kenneth I. Welsh, Roland M. du Bois, and Jules M.M. van den Bosch
Respiration, 2006, Volume 73, Number 5, Page 623
Medicine & Science in Sports & Exercise, 2006, Volume 38, Number 6, Page 1074
Manfred Sch??rmann
American Journal of PharmacoGenomics, 2003, Volume 3, Number 4, Page 233
Medicine & Science in Sports & Exercise, 2004, Volume 36, Number 8, Page 1314

Comments (0)

Please log in or register to comment.
Log in