PMID- 17940859
OWN - NLM
STAT- MEDLINE
DCOM- 20080215
LR  - 20181201
IS  - 0920-3206 (Print)
IS  - 0920-3206 (Linking)
VI  - 21
IP  - 6
DP  - 2007 Dec
TI  - Effect of long-term monotherapy with the aldosterone receptor blocker eplerenone 
      on cytoskeletal proteins and matrix metalloproteinases in dogs with heart 
      failure.
PG  - 415-22
AB  - PURPOSE: Long-term monotherapy with the aldosterone receptor blocker eplerenone 
      in dogs with HF was previously shown to improve LV systolic and diastolic 
      function. This study examined the effects of long-term monotherapy with the 
      aldosterone receptor blocker eplerenone on mRNA and protein expression of the 
      cytoskeletal proteins titin, tubulin, fibronectin and vimentin, the matrix 
      metalloproteinases (MMPs)-1, -2 and -9, and the tissue inhibitors of MMPs 
      (TIMPs)-1 and -2 in left ventricular (LV) myocardium of dogs with heart failure 
      (HF). METHODS: HF was produced in 12 dogs by intracoronary microembolizations. 
      Dogs were randomized to 3 months oral therapy with eplerenone (10 mg/kg twice 
      daily, n = 6) or to no therapy at all (HF-control, n = 6). LV tissue from six 
      normal dogs was used for comparison. mRNA expression was measured using 
      reverse-transcriptase polymerase chain reaction (RT-PCR) and protein expression 
      using Western blots. RESULTS: Compared to NL dogs, control dogs showed 
      upregulation of mRNA and protein expression for tubulin, fibronectin, MMP-1, -2 
      and -9, and down-regulation of mRNA and protein expression for total titin. 
      Normalization of mRNA and protein expression for all these genes was seen after 
      treatment with eplerenone. N2BA/N2B-titin mRNA expression ratio increased 
      significantly in dogs with HF treated with eplerenone. No differences in 
      expression for vimentin, TIMP-1 and -2 were observed among groups. CONCLUSIONS: 
      In dogs with HF, long-term eplerenone therapy normalizes mRNA and protein 
      expression of key cytoskeletal proteins and MMPs. Reversal of these molecular 
      maladaptations may partly explain the improvement in LV diastolic function seen 
      after long-term therapy with eplerenone.
FAU - Rastogi, Sharad
AU  - Rastogi S
AD  - Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Health 
      System, Detroit, MI 48202, USA.
FAU - Mishra, Sudhish
AU  - Mishra S
FAU - Zaca, Valerio
AU  - Zaca V
FAU - Alesh, Issa
AU  - Alesh I
FAU - Gupta, Ramesh C
AU  - Gupta RC
FAU - Goldstein, Sidney
AU  - Goldstein S
FAU - Sabbah, Hani N
AU  - Sabbah HN
LA  - eng
GR  - P01 HL074237-04/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Cardiovasc Drugs Ther
JT  - Cardiovascular drugs and therapy
JID - 8712220
RN  - 0 (Angiotensin-Converting Enzyme Inhibitors)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Mineralocorticoid Receptor Antagonists)
RN  - 0 (RNA, Messenger)
RN  - 0 (Tissue Inhibitor of Metalloproteinase-1)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 27O7W4T232 (Spironolactone)
RN  - 6995V82D0B (Eplerenone)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
SB  - IM
MH  - Angiotensin-Converting Enzyme Inhibitors/therapeutic use
MH  - Animals
MH  - Cytoskeletal Proteins/*genetics
MH  - Dogs
MH  - Eplerenone
MH  - Heart Failure/*drug therapy/metabolism
MH  - Matrix Metalloproteinases/genetics
MH  - *Mineralocorticoid Receptor Antagonists/*pharmacology
MH  - RNA, Messenger/analysis
MH  - Spironolactone/*analogs & derivatives/pharmacology
MH  - Tissue Inhibitor of Metalloproteinase-1/genetics
MH  - Tissue Inhibitor of Metalloproteinase-2/genetics
EDAT- 2007/10/18 09:00
MHDA- 2008/02/19 09:00
CRDT- 2007/10/18 09:00
PHST- 2007/10/18 09:00 [pubmed]
PHST- 2008/02/19 09:00 [medline]
PHST- 2007/10/18 09:00 [entrez]
AID - 10.1007/s10557-007-6057-8 [doi]
PST - ppublish
SO  - Cardiovasc Drugs Ther. 2007 Dec;21(6):415-22. doi: 10.1007/s10557-007-6057-8.