Linked Life Data

21189404

Source:http://linkedlifedata.com/resource/pubmed/id/21189404

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-20
pubmed:abstractText
Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase capable of metabolizing angiotensin (Ang) II into Ang 1 to 7. We hypothesized that ACE2 is a negative regulator of Ang II signaling and its adverse effects on the kidneys. Ang II infusion (1.5 mg/kg?¹/d?¹) for 4 days resulted in higher renal Ang II levels and increased nicotinamide adenine dinucleotide phosphate oxidase activity in ACE2 knockout (Ace2(-/y)) mice compared to wild-type mice. Expression of proinflammatory cytokines, interleukin-1? and chemokine (C-C motif) ligand 5, were increased in association with greater activation of extracellular-regulated kinase 1/2 and increase of protein kinase C-? levels. These changes were associated with increased expression of fibrosis-associated genes (?-smooth muscle actin, transforming growth factor-?, procollagen type I?1) and increased protein levels of collagen I with histological evidence of increased tubulointerstitial fibrosis. Ang II-infused wild-type mice were then treated with recombinant human ACE2 (2 mg/kg?¹/d?¹, intraperitoneal). Daily treatment with recombinant human ACE2 reduced Ang II-induced pressor response and normalized renal Ang II levels and oxidative stress. These changes were associated with a suppression of Ang II-mediated activation of extracellular-regulated kinase 1/2 and protein kinase C pathway and Ang II-mediated renal fibrosis and T-lymphocyte-mediated inflammation. We conclude that loss of ACE2 enhances renal Ang II levels and Ang II-induced renal oxidative stress, resulting in greater renal injury, whereas recombinant human ACE2 prevents Ang II-induced hypertension, renal oxidative stress, and tubulointerstitial fibrosis. ACE2 is an important negative regulator of Ang II-induced renal disease and enhancing ACE2 action may have therapeutic potential for patients with kidney disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
57
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
314-22
pubmed:meshHeading
pubmed-meshheading:21189404-Actins, pubmed-meshheading:21189404-Angiotensin II, pubmed-meshheading:21189404-Animals, pubmed-meshheading:21189404-Blotting, Western, pubmed-meshheading:21189404-Collagen, pubmed-meshheading:21189404-Cytokines, pubmed-meshheading:21189404-Female, pubmed-meshheading:21189404-Fibrosis, pubmed-meshheading:21189404-Gene Expression, pubmed-meshheading:21189404-Humans, pubmed-meshheading:21189404-Immunohistochemistry, pubmed-meshheading:21189404-Inflammation, pubmed-meshheading:21189404-Kidney, pubmed-meshheading:21189404-Male, pubmed-meshheading:21189404-Mice, pubmed-meshheading:21189404-Mice, Inbred C57BL, pubmed-meshheading:21189404-Mice, Knockout, pubmed-meshheading:21189404-Muscle, Smooth, pubmed-meshheading:21189404-NADPH Oxidase, pubmed-meshheading:21189404-Oxidative Stress, pubmed-meshheading:21189404-Peptidyl-Dipeptidase A, pubmed-meshheading:21189404-Recombinant Proteins, pubmed-meshheading:21189404-Reverse Transcriptase Polymerase Chain Reaction
pubmed:year
2011
pubmed:articleTitle
Prevention of angiotensin II-mediated renal oxidative stress, inflammation, and fibrosis by angiotensin-converting enzyme 2.
pubmed:affiliation
Division of Cardiology, Department of Medicine, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't