PMID- 17678740
OWN - NLM
STAT- MEDLINE
DCOM- 20070924
LR  - 20161124
IS  - 1558-3597 (Electronic)
IS  - 0735-1097 (Linking)
VI  - 50
IP  - 6
DP  - 2007 Aug 7
TI  - Chronic monotherapy with rosuvastatin prevents progressive left ventricular 
      dysfunction and remodeling in dogs with heart failure.
PG  - 551-7
AB  - OBJECTIVES: This study examined the effects of long-term monotherapy with 
      rosuvastatin (RSV) on the progression of left ventricular (LV) dysfunction and 
      remodeling in dogs with heart failure (HF). BACKGROUND: 
      3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors or "statins" possess 
      other noncholesterol-lowering properties that include inhibiting proinflammatory 
      cytokines, attenuating LV hypertrophy, and stimulating the release of bone 
      marrow-derived stem cells (BMSCs). METHODS: Twenty-one dogs with 
      microembolization-induced HF were randomized to 3 months oral monotherapy with 
      low-dose (LD) RSV (0.5 mg/kg once daily, n = 7), high-dose (HD) RSV (3.0 mg/kg 
      once daily, n = 7), or to no therapy (control group, n = 7). The change (Delta) 
      from pre- to post-therapy (treatment effect) in LV end-diastolic volume (EDV) and 
      end-systolic volume (ESV) and ejection fraction (EF) was measured. Protein level 
      of tumor necrosis factor (TNF)-alpha in LV tissue and the number of circulating 
      Sca-1-positive BMSCs was also determined. Blood and LV tissue from 6 normal dogs 
      was obtained and used for comparison. RESULTS: There were no differences in 
      DeltaEDV, DeltaESV, and DeltaEF between control group and LD RSV. In contrast, 
      DeltaEDV and DeltaESV were significantly lower, and DeltaEF was significantly 
      higher in HD RSV compared with control group. High-dose, but not LD, RSV also 
      normalized protein levels of TNF-alpha and was associated with a significant 
      increase in the number of circulating BMSCs. CONCLUSIONS: In dogs with HF, 
      chronic therapy with HD RSV prevents progressive LV dysfunction and dilation. 
      This benefit may be partly derived from normalization of TNF-alpha expression and 
      partly from increased mobilization of BMSCs.
FAU - Zaca, Valerio
AU  - Zaca V
AD  - Department of Medicine, Division of Cardiovascular Medicine, Henry Ford Heart and 
      Vascular Institute, Henry Ford Health System, Detroit, Michigan, USA.
FAU - Rastogi, Sharad
AU  - Rastogi S
FAU - Imai, Makoto
AU  - Imai M
FAU - Wang, Mengjun
AU  - Wang M
FAU - Sharov, Victor G
AU  - Sharov VG
FAU - Jiang, Alice
AU  - Jiang A
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
PT  - Research Support, Non-U.S. Gov't
DEP - 20070723
PL  - United States
TA  - J Am Coll Cardiol
JT  - Journal of the American College of Cardiology
JID - 8301365
RN  - 0 (Fluorobenzenes)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0 (Pyrimidines)
RN  - 0 (Sulfonamides)
RN  - 0 (Tumor Necrosis Factor-alpha)
RN  - 83MVU38M7Q (Rosuvastatin Calcium)
RN  - EC 3.4.24.24 (Matrix Metalloproteinase 2)
SB  - IM
MH  - Animals
MH  - Coronary Angiography
MH  - Dogs
MH  - Fluorobenzenes/*administration & dosage
MH  - Heart Failure/diagnostic imaging/*drug therapy/pathology
MH  - Hematopoietic Stem Cells/metabolism
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage
MH  - Matrix Metalloproteinase 2/metabolism
MH  - Myocardium/metabolism/pathology
MH  - Pyrimidines/*administration & dosage
MH  - Rosuvastatin Calcium
MH  - Sulfonamides/*administration & dosage
MH  - Treatment Outcome
MH  - Tumor Necrosis Factor-alpha/metabolism
MH  - Ventricular Dysfunction, Left/diagnostic imaging/*drug therapy/pathology
MH  - Ventricular Remodeling/*drug effects
EDAT- 2007/08/07 09:00
MHDA- 2007/09/25 09:00
CRDT- 2007/08/07 09:00
PHST- 2006/11/27 00:00 [received]
PHST- 2007/04/09 00:00 [revised]
PHST- 2007/04/10 00:00 [accepted]
PHST- 2007/08/07 09:00 [pubmed]
PHST- 2007/09/25 09:00 [medline]
PHST- 2007/08/07 09:00 [entrez]
AID - S0735-1097(07)01600-2 [pii]
AID - 10.1016/j.jacc.2007.04.050 [doi]
PST - ppublish
SO  - J Am Coll Cardiol. 2007 Aug 7;50(6):551-7. doi: 10.1016/j.jacc.2007.04.050. Epub 
      2007 Jul 23.