RGD Reference Report - Targeting the renin-angiotensin system: what's new? - Rat Genome Database

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Targeting the renin-angiotensin system: what's new?

Authors: Leckie, BJ 
Citation: Leckie BJ Curr Med Chem Cardiovasc Hematol Agents. 2005 Jan;3(1):23-32.
RGD ID: 1581742
Pubmed: PMID:15638741   (View Abstract at PubMed)

The renin-angiotensin system is a key target for drugs combating cardiovascular disease. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor type-1 (AT1 receptor) blockers are well known. However, angiotensin peptides can be generated through a number of pathways besides the classic system. This review outlines some of these pathways, their relation to the classic system and the likely effect of inhibiting them. Renin is still the key enzyme in angiotensin peptide generation and seems to be the only route to angiotensin I formation in vivo. Renin inhibitors may have some advantages in terms of specificity. Also, by blocking angiotensin I generation, the production of downstream bioactive angiotensin I metabolites should also be blocked. Chymase, a mast cell serine protease, cleaves angiotensin I to produce angiotensin II and may be important at sites of inflammation such as atherosclerotic plaque. Angiotensin-converting enzyme 2 (ACE2), a carboxypeptidase structurally related to ACE but resistant to ACE inhibitors, has a protective effect on cardiac function. Neutral endopeptidase 24.11 breaks down both atrial natriuretic peptide and angiotensin II. Inhibiting it potentiates the action of endogenous atrial peptide but only affects circulating angiotensin II when basal levels are above normal. Dual inhibitors of ACE and endopeptidase 24.11 may be of value where there is both sodium retention and increased angiotensin II. Targeting the renin-angiotensin system by gene therapy or antibody treatment may provide a longer-term treatment for hypertension.



RGD Manual Annotations

1 to 20 of 33 rows

  
Object Symbol
Species
Term
Qualifier
Evidence
With
Notes
Source
Original Reference(s)
ACE2Humanangiotensin (1-7) signaling pathway  TAS  RGD 
MMEHumanangiotensin (1-7) signaling pathway  TAS  RGD 
MmeMouseangiotensin (1-7) signaling pathway  ISOMME (Homo sapiens) RGD 
MmeRatangiotensin (1-7) signaling pathway  ISOMME (Homo sapiens) RGD 
ACEHumanangiotensin II signaling pathway   TAS  RGD 
AceRatangiotensin II signaling pathway   ISOACE (Homo sapiens) RGD 
AceMouseangiotensin II signaling pathway   ISOACE (Homo sapiens) RGD 
CMA1Humanangiotensin II signaling pathway   TAS  RGD 
ENPEPHumanangiotensin III signaling pathway  TAS  RGD 
ANPEPHumanangiotensin IV signaling pathway  TAS  RGD 
ACEHumanrenin-angiotensin cascade pathway   TAS  RGD 
ACE2Humanrenin-angiotensin cascade pathway   TAS  RGD 
AGTHumanrenin-angiotensin cascade pathway   TAS  RGD 
ANPEPHumanrenin-angiotensin cascade pathway   TAS  RGD 
AceMouserenin-angiotensin cascade pathway   ISOACE (Homo sapiens) RGD 
AceRatrenin-angiotensin cascade pathway   ISOACE (Homo sapiens) RGD 
Ace2Ratrenin-angiotensin cascade pathway   ISOACE2 (Homo sapiens) RGD 
Ace2Mouserenin-angiotensin cascade pathway   ISOACE2 (Homo sapiens) RGD 
AgtRatrenin-angiotensin cascade pathway   ISOAGT (Homo sapiens) RGD 
AgtMouserenin-angiotensin cascade pathway   ISOAGT (Homo sapiens) RGD 
1 to 20 of 33 rows

Genes (Rattus norvegicus)
Ace  (angiotensin I converting enzyme) Ace2  (angiotensin converting enzyme 2) Agt  (angiotensinogen)
Cma1  (chymase 1) Enpep  (glutamyl aminopeptidase) Mme  (membrane metallo-endopeptidase)
Ren  (renin)

Genes (Mus musculus)
Ace  (angiotensin I converting enzyme) Ace2  (angiotensin converting enzyme 2) Agt  (angiotensinogen)
Anpep  (alanyl aminopeptidase, membrane) Cma1  (chymase 1, mast cell) Enpep  (glutamyl aminopeptidase)
Mme  (membrane metallo endopeptidase) Ren1  (renin 1 structural)

Genes (Homo sapiens)
ACE  (angiotensin I converting enzyme) ACE2  (angiotensin converting enzyme 2) AGT  (angiotensinogen)
ANPEP  (alanyl aminopeptidase, membrane) CMA1  (chymase 1) ENPEP  (glutamyl aminopeptidase)
MME  (membrane metalloendopeptidase) REN  (renin)

Gene Anpep alanyl aminopeptidase, membrane Rattus norvegicus