RGD Reference Report - Novel mechanism and role of angiotensin II induced vascular endothelial injury in hypertensive diastolic heart failure. - Rat Genome Database

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Novel mechanism and role of angiotensin II induced vascular endothelial injury in hypertensive diastolic heart failure.

Authors: Yamamoto, E  Kataoka, K  Shintaku, H  Yamashita, T  Tokutomi, Y  Dong, YF  Matsuba, S  Ichijo, H  Ogawa, H  Kim-Mitsuyama, S 
Citation: Yamamoto E, etal., Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2569-75. Epub 2007 Oct 11.
RGD ID: 10412644
Pubmed: PMID:17932313   (View Abstract at PubMed)
DOI: DOI:10.1161/ATVBAHA.107.153692   (Journal Full-text)

OBJECTIVE: The mechanism and role of angiotensin II-induced vascular endothelial injury is unclear. We examined the molecular mechanism of angiotensin (AII)-induced vascular endothelial injury and its significance for hypertensive diastolic heart failure. METHODS AND RESULTS: We compared the effect of valsartan and amlodipine on Dahl salt-sensitive hypertensive rats (DS rats). Valsartan improved vascular endothelial dysfunction of DS rats more than amlodipine, by inhibiting endothelial apoptosis and eNOS uncoupling more. Moreover, valsartan inhibited vascular apoptosis signal-regulating kinase 1 (ASK1) more than amlodipine. Thus, AT1 receptor contributed to vascular endothelial apoptosis, eNOS uncoupling, and ASK1 activation of DS rats. Using ASK1(-/-) mice, we examined the causative role of ASK1 in endothelial apoptosis and eNOS uncoupling. AII infusion in wild-type mice markedly caused vascular endothelial apoptosis and eNOS uncoupling accompanied by vascular endothelial dysfunction, whereas these effects of AII were absent in ASK1(-/-) mice. Therefore, ASK1 participated in AII-induced vascular endothelial apoptosis and eNOS uncoupling. Using tetrahydrobiopterin, we found that eNOS uncoupling was involved in vascular endothelial dysfunction in DS rats with established diastolic heart failure. CONCLUSIONS: AII-induced vascular endothelial apoptosis and eNOS uncoupling were mediated by ASK1 and contributed to vascular injury in diastolic heart failure of salt-sensitive hypertension.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Map3k5Ratendothelial cell apoptotic process  IEP  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Map3k5  (mitogen-activated protein kinase kinase kinase 5)


Additional Information