PMID- 17449418
OWN - NLM
STAT- MEDLINE
DCOM- 20070511
LR  - 20131121
IS  - 1557-3117 (Electronic)
IS  - 1053-2498 (Linking)
VI  - 26
IP  - 5
DP  - 2007 May
TI  - Inhibition of chemokine receptor CCR2 and CCR5 expression contributes to 
      simvastatin-induced attenuation of cardiac allograft vasculopathy.
PG  - 485-93
AB  - BACKGROUND: Accumulating evidence reveals that statins possess pleiotropic 
      properties beyond cholesterol reduction, which may contribute to the attenuation 
      of cardiac allograft vasculopathy (CAV). Recent in vitro data suggest that 
      statins could down-regulate chemokine receptors. This study was designed to test 
      the hypothesis that simvastatin ameliorates CAV development via the inhibition of 
      chemokine receptor expression in an inbred rat model of cardiac transplantation. 
      METHODS: Animals were divided into four groups: isograft; control (cyclosporine 
      [CsA] + vehicle); low-dose simvastatin (LSIM; CsA + 5 mg/kg simvastatin); and 
      high-dose simvastatin (HSIM; CsA + 10 mg/kg simvastatin). Donor hearts from 
      Fisher 344 rats were transplanted heterotopically into Lewis rat recipients. CsA 
      was administered at 1.5 mg/kg/day for 2 weeks post-operatively. In addition, 
      recipients were treated daily with simvastatin or vehicle for 8 weeks. Donor 
      hearts were harvested for histopathologic and immunohistochemical examination. 
      Intragraft concentration of chemokines and chemokine receptor expression were 
      analyzed using enzyme-linked immunosorbent assay and quantitative real-time 
      polymerase chain reaction, respectively. RESULTS: Both low and high doses of 
      simvastatin significantly decreased the CAV score; inhibited recruitment of T 
      lymphocytes and macrophages; reduced levels of intragraft MCP-1 (monocyte 
      chemoattractant protein-1), RANTES (regulated on activation, normal T-cell 
      expressed and secreted) protein and IP-10 (interferon-inducible protein-10); and 
      down-regulated expression of chemokine receptors CCR2 and CCR5. CXCR3 expression 
      was not affected by simvastatin treatment. CONCLUSIONS: Our results demonstrate 
      that simvastatin may attenuate CAV development, possibly through retarding 
      intragraft chemokine accumulation and chemokine receptor expression.
FAU - Yin, Rong
AU  - Yin R
AD  - Department of Cardiothoracic Surgery, Jinling Hospital, Clinical Medicine School 
      of Nanjing University, Nanjing, China.
FAU - Zhu, Jiaquan
AU  - Zhu J
FAU - Shao, Hongtao
AU  - Shao H
FAU - Cheng, Xiaofeng
AU  - Cheng X
FAU - Feng, Xiaomei
AU  - Feng X
FAU - Li, Zhongdong
AU  - Li Z
FAU - Jing, Hua
AU  - Jing H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Heart Lung Transplant
JT  - The Journal of heart and lung transplantation : the official publication of the 
      International Society for Heart Transplantation
JID - 9102703
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CCL5)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, CCR5)
RN  - 0 (Receptors, Chemokine)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Animals
MH  - Chemokine CCL2/drug effects/metabolism
MH  - Chemokine CCL5/metabolism
MH  - Disease Models, Animal
MH  - Down-Regulation
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Graft Rejection/pathology/*prevention & control
MH  - *Heart Transplantation
MH  - Immunohistochemistry
MH  - Male
MH  - RNA, Messenger/analysis
MH  - Random Allocation
MH  - Rats
MH  - Rats, Inbred F344
MH  - Receptors, CCR5/drug effects/metabolism
MH  - Receptors, Chemokine/*drug effects/*metabolism
MH  - Reference Values
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Sensitivity and Specificity
MH  - Simvastatin/*pharmacology
MH  - Transplantation, Homologous
EDAT- 2007/04/24 09:00
MHDA- 2007/05/12 09:00
CRDT- 2007/04/24 09:00
PHST- 2006/12/22 00:00 [received]
PHST- 2007/01/26 00:00 [revised]
PHST- 2007/02/03 00:00 [accepted]
PHST- 2007/04/24 09:00 [pubmed]
PHST- 2007/05/12 09:00 [medline]
PHST- 2007/04/24 09:00 [entrez]
AID - S1053-2498(07)00195-7 [pii]
AID - 10.1016/j.healun.2007.02.006 [doi]
PST - ppublish
SO  - J Heart Lung Transplant. 2007 May;26(5):485-93. doi: 
      10.1016/j.healun.2007.02.006.