Linked Life Data

14581293

Source:http://linkedlifedata.com/resource/pubmed/id/14581293

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-12-12
pubmed:abstractText
N-acetyl-seryl-aspartyl-lysyl-proline (Ac-SDKP) is a natural substrate for the N-terminal active site of angiotensin-converting enzyme (ACE). We previously reported that Ac-SDKP prevented cardiac fibrosis in rats with renovascular or aldosterone-salt hypertension. However, it is not clear whether Ac-SDKP reverses cardiac fibrosis in hypertension, nor the mechanism(s) involved. In the present study, we tested the hypothesis that Ac-SDKP reversal of hypertension-induced cardiac fibrosis involves a decrease in transforming growth factor-beta (TGF-beta) and/or connective tissue growth factor (CTGF). In 2-kidney, 1-clip (2K-1C) hypertensive rats, Ac-SDKP at 400 or 800 microg/kg per day SC was started 8 weeks after hypertension and cardiac fibrosis were established and was continued for 8 weeks. Left ventricular (LV) collagen in rats with 2K-1C plus vehicle at 8 and 16 weeks after clipping was similar but higher than in the sham group (P<0.05). Ac-SDKP at 400 and 800 microg/kg per day, which increased plasma Ac-SDKP 2- and 5-fold, respectively, reversed the increase in LV collagen in a dose-dependent manner. The mechanism by which Ac-SDKP reverses LV fibrosis does not appear to depend on ACE inhibition by Ac-SDKP, since we found that Ac-SDKP at various doses did not affect blood pressure responses to exogenous angiotensin I or bradykinin. However, Ac-SDKP reversed the increase in LV TGF-beta and CTGF compared with rats with 2K-1C plus vehicle (P<0.005). We concluded that in hypertension, Ac-SDKP reverses cardiac fibrosis, perhaps due in part to a decrease in TGF-beta and CTGF in the heart.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1524-4563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
42
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1164-70
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:14581293-Angiotensins, pubmed-meshheading:14581293-Animals, pubmed-meshheading:14581293-Blood Pressure, pubmed-meshheading:14581293-Body Weight, pubmed-meshheading:14581293-Bradykinin, pubmed-meshheading:14581293-Collagen, pubmed-meshheading:14581293-Connective Tissue Growth Factor, pubmed-meshheading:14581293-Fibrosis, pubmed-meshheading:14581293-Heart Ventricles, pubmed-meshheading:14581293-Hypertension, Renovascular, pubmed-meshheading:14581293-Immediate-Early Proteins, pubmed-meshheading:14581293-Intercellular Signaling Peptides and Proteins, pubmed-meshheading:14581293-Male, pubmed-meshheading:14581293-Myocardium, pubmed-meshheading:14581293-Oligopeptides, pubmed-meshheading:14581293-Organ Size, pubmed-meshheading:14581293-Rats, pubmed-meshheading:14581293-Rats, Sprague-Dawley, pubmed-meshheading:14581293-Transforming Growth Factor beta
pubmed:year
2003
pubmed:articleTitle
Ac-SDKP reverses cardiac fibrosis in rats with renovascular hypertension.
pubmed:affiliation
Hypertension and Vascular Research Division, Henry Ford Hospital, Detroit, Mich 48202-2689, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't