RGD Reference Report - Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats: involvement of ACE2-Ang (1-7)-mas axis. - Rat Genome Database

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Candesartan cilexetil protects from cardiac myosin induced cardiotoxicity via reduction of endoplasmic reticulum stress and apoptosis in rats: involvement of ACE2-Ang (1-7)-mas axis.

Authors: Arumugam, S  Thandavarayan, RA  Palaniyandi, SS  Giridharan, VV  Arozal, W  Sari, FR  Soetikno, V  Harima, M  Suzuki, K  Kodama, M  Watanabe, K 
Citation: Arumugam S, etal., Toxicology. 2012 Jan 27;291(1-3):139-45. doi: 10.1016/j.tox.2011.11.008. Epub 2011 Nov 23.
RGD ID: 8549486
Pubmed: PMID:22120037   (View Abstract at PubMed)
DOI: DOI:10.1016/j.tox.2011.11.008   (Journal Full-text)

Candesartan cilexetil, an angiotensin (Ang) II receptor 1 blocker was reported to suppress the myocardial damage in various cardiovascular complications but the mode by which it is effective in preventing the progression of dilated cardiomyopathy (DCM) is unknown. Emerging evidences suggest that, at least, part of the benefits observed with the use of AT1 receptor blockers could be attributed to the increased Ang (1-7) levels observed during administration of these agents. Identification of the novel components of the RAS, ACE2 and Ang (1-7) receptor mas, provided essential elements for considering the existence of a vasodilator arm of the RAS, represented by the ACE2-Ang (1-7)-mas axis. In this study, rat model of DCM was prepared by injection with porcine cardiac myosin. Twenty-eight days after immunization, candesartan cilexetil was administered intraperitoneally at 1 or 10mg/kg/day to rats for four weeks. Myocardial expression of Ang receptors and markers of calcium homeostasis, endoplasmic reticulum (ER) stress and apoptosis were measured by Western blotting and histopathological staining techniques. Candesartan improved the functional markers in a dose-dependent manner and also upregulated Ang (1-7), ACE2 and mas1 in the myocardium of DCM rats. Various ER stress and apoptosis markers were attenuated and the number apoptotic cells were significantly lower in the candesartan treated rats compared with those of the vehicle group. These findings suggest that candesartan treatment prevented the progression of DCM by activation of the counter regulatory arm of the RAS and possibly through modulation of ER stress and subsequently, cardiac apoptosis.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AGTHumandilated cardiomyopathy treatmentISOAgt (Rattus norvegicus) RGD 
AGTR1Humandilated cardiomyopathy treatmentISOAgtr1a (Rattus norvegicus) RGD 
AGTR2Humandilated cardiomyopathy  ISOAgtr2 (Rattus norvegicus)protein:increased expression:heartRGD 
AgtRatdilated cardiomyopathy treatmentIEP  RGD 
AgtMousedilated cardiomyopathy treatmentISOAgt (Rattus norvegicus) RGD 
Agtr1aRatdilated cardiomyopathy treatmentIEP  RGD 
Agtr1aMousedilated cardiomyopathy treatmentISOAgtr1a (Rattus norvegicus) RGD 
Agtr2Ratdilated cardiomyopathy  IEP protein:increased expression:heartRGD 
Agtr2Mousedilated cardiomyopathy  ISOAgtr2 (Rattus norvegicus)protein:increased expression:heartRGD 
MAS1Humandilated cardiomyopathy treatmentISOMas1 (Rattus norvegicus) RGD 
Mas1Ratdilated cardiomyopathy treatmentIEP  RGD 
Mas1Mousedilated cardiomyopathy treatmentISOMas1 (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Agt  (angiotensinogen)
Agtr1a  (angiotensin II receptor, type 1a)
Agtr2  (angiotensin II receptor, type 2)
Mas1  (MAS1 proto-oncogene, G protein-coupled receptor)

Genes (Mus musculus)
Agt  (angiotensinogen)
Agtr1a  (angiotensin II receptor, type 1a)
Agtr2  (angiotensin II receptor, type 2)
Mas1  (MAS1 oncogene)

Genes (Homo sapiens)
AGT  (angiotensinogen)
AGTR1  (angiotensin II receptor type 1)
AGTR2  (angiotensin II receptor type 2)
MAS1  (MAS1 proto-oncogene, G protein-coupled receptor)


Additional Information