Therapeutic targeting of the angiotensin-converting enzyme 2/Angiotensin-(1-7)/Mas cascade in the renin-angiotensin system: a patent review

被引:39
作者
Ferreira, Anderson J. [3 ]
Bader, Michael [1 ,2 ,4 ]
Santos, Robson A. S. [3 ]
机构
[1] Max Delbruck Ctr Mol Med MDC, D-13092 Berlin, Germany
[2] Univ Fed Minas Gerais, Inst Biol Sci, Dept Morphol, BR-31270901 Belo Horizonte, MG, Brazil
[3] Univ Fed Minas Gerais, Inst Biol Sci, Natl Inst Sci & Technol Nanobiopharmaceut, Dept Physiol & Biophys, BR-31270901 Belo Horizonte, MG, Brazil
[4] Max Delbruck Ctr Mol Med, D-13125 Berlin, Germany
关键词
ACE2; activators; Angiotensin II; Angiotensin-(1-7) formulations; cardiovascular diseases; Mas agonists; RECEPTOR MAS AGONIST; MIMIC AVE-0991; HEART-FAILURE; PEPTIDE; BLOCKADE; HYPERTENSION; MODULATION; LIPOSOMES; PROTECTS; LOSARTAN;
D O I
10.1517/13543776.2012.682572
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Introduction: The renin-angiotensin system (RAS) is a main therapeutic target for cardiovascular diseases. Within the last two decades, novel components of the RAS have been discovered, opening new opportunities to interfere with its activity. Angiotensin(Ang)-(1-7) is synthesized by angiotensin-converting enzyme 2 (ACE2), and interacts with the G-protein-coupled receptor Mas. The axis formed by ACE2/Ang-(1-7)/Mas represents an endogenous counter regulatory pathway within the RAS. Areas covered: In this review, the authors discuss patents and recent initiatives to develop therapeutic strategies based on the ACE2/Ang-(1-7)/Mas axis. Expert opinion: Many publications and patents support a strategy to interfere with the activity of the RAS by stimulating its counter-regulatory axis mainly in two different ways: i) To increase the activity of ACE2, which will impact the system by increasing the inactivation of Ang II and the production of Ang-(1-7); ii) To stimulate Mas, taking advantage of nanostructured formulations of the natural peptide or analogues of Ang-(1-7). Although the preclinical studies are compelling, the possible impact of these novel therapeutic tools for the treatment of cardiometabolic diseases will only be known after completion of the ongoing clinical studies.
引用
收藏
页码:567 / 574
页数:8
相关论文
共 70 条
[1]   Tissue Renin-Angiotensin-Aldosterone Systems: Targets for Pharmacological Therapy [J].
Bader, Michael .
ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY, 2010, 50 :439-465
[2]   Angiotensin-(1-7) Blockade Attenuates Captopril- or Hydralazine-induced Cardiovascular Protection in Spontaneously Hypertensive Rats Treated With NG-nitro-L-Arginine Methyl Ester [J].
Benter, Ibrahim F. ;
Yousif, Mariam H. M. ;
Al-Saleh, Fatemah M. ;
Raghupathy, Raj ;
Chappell, Mark C. ;
Diz, Debra I. .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 2011, 57 (05) :559-567
[3]   Angiotensin-(1-7) prevents development of severe hypertension and end-organ damage in spontaneously hypertensive rats treated with L-NAME [J].
Benter, IF ;
Yousif, MHM ;
Anim, JT ;
Cojocel, C ;
Diz, DI .
AMERICAN JOURNAL OF PHYSIOLOGY-HEART AND CIRCULATORY PHYSIOLOGY, 2006, 290 (02) :H684-H691
[4]   Role of angiotensin-(1-7) in the modulation of the baroreflex in renovascular hypertensive rats [J].
Britto, RR ;
Santos, RAS ;
FagundesMoura, CR ;
Khosla, MC ;
CampagnoleSantos, MJ .
HYPERTENSION, 1997, 30 (03) :549-556
[5]   CONVERTING-ENZYME INHIBITION AND ITS WITHDRAWAL IN SPONTANEOUSLY HYPERTENSIVE RATS [J].
CAMPBELL, DJ ;
DUNCAN, AM ;
KLADIS, A ;
HARRAP, SB .
JOURNAL OF CARDIOVASCULAR PHARMACOLOGY, 1995, 26 (03) :426-436
[6]   Evidence for mas-mediated bradykinin potentiation by the angiotensin-(1-7) nonpeptide mimic AVE 0991 in normotensive rats [J].
Carvalho, Mariana B. L. ;
Duarte, Fernanda V. ;
Faria-Silva, Raphael ;
Fauler, Beatrix ;
Machado, Leonor T. Da Mata ;
de Paula, Renata D. ;
Campagnole-Santos, Maria J. ;
Santos, Robson A. S. .
HYPERTENSION, 2007, 50 (04) :762-767
[7]   Metabolism of angiotension-(1-7) by angiotensin-converting enzyme [J].
Chappell, MC ;
Pirro, NT ;
Sykes, A ;
Ferrario, CM .
HYPERTENSION, 1998, 31 (01) :362-367
[8]  
Cohen Y, 2011, Peptides which bind to G protein-coupled receptors, Patent No. [US7884180, 7884180]
[9]   The role of Ang (1-7) in mediating the chronic hypotensive effects of losartan in normal rats [J].
Collister, JP ;
Hendel, MD .
JOURNAL OF THE RENIN-ANGIOTENSIN-ALDOSTERONE SYSTEM, 2003, 4 (03) :176-179
[10]   The Effect of the Thioether-Bridged, Stabilized Angiotensin-(1-7) Analogue Cyclic Ang-(1-7) on Cardiac Remodeling and Endothelial Function in Rats with Myocardial Infarction [J].
Durik, Matej ;
van Veghel, Richard ;
Kuipers, Anneke ;
Rink, Rick ;
Akanbi, Marijke Haas Jimoh ;
Moll, Gert ;
Danser, A. H. Jan ;
Roks, Anton J. M. .
INTERNATIONAL JOURNAL OF HYPERTENSION, 2012, 2012