title: CC chemokine CCL5 plays a central role impacting infarct size and post-infarction heart failure in mice.
abstract: OBJECTIVE
  The chemokine CCL5 plays a critical role as neutrophil and macrophage activator do in atherosclerosis and myocardial infarction. Thus, we investigated whether the treatment with a neutralizing monoclonal antibody (mAb) to mouse CCL5 would provide therapeutic benefit when provoking a coronary-associated ischaemic event.
  
  
  RESULTS
  C57Bl/6 mice were submitted to left coronary artery permanent ligature. Then, various parameters were monitored for up to 21 days. At5 min and 3 days after coronary occlusion, mice received one intravenous injection of the rat anti-mouse CCL5 mAb or isotype IgG control. Infarct size was assessed histologically and by measuring serum cardiac troponin I levels. Kinetics of CCL5 tissue expression, leucocyte infiltration, matrix metalloproteinase (MMP) levels, and collagen deposition were histologically assessed. Serum chemokine levels were measured by enzyme-linked immunosorbent assay. Cardiac function and dimensions were assessed by magnetic resonance imaging (MRI). Chronic ischaemia increased both circulating and intracardiac levels of CCL5. At 24 h, treatment with the anti-CCL5 mAb resulted in a smaller infarct size and reduced circulating levels of chemokines. This effect was associated with reduction of neutrophil and macrophage infiltration within the infarcted myocardium. After 3 days of chronic ischaemia, anti-CCL5 mAb treatment reduced cardiac MMP-9. At 7 days, collagen content was significantly lower. At 21 days, neutralizing CCL5 improved mouse survival, cardiac myocyte size, and cardiac function.
  
  
  CONCLUSIONS
  Treatment with anti-CCL5 mAb significantly reduced both infarct size and post-infarction heart failure in a mouse model of chronic cardiac ischaemia. Cardioprotective effects were associated with the reduction of leucocyte recruitment within infarcted hearts.
authors: Division of Cardiology, Foundation for Medical Researches, Department of Internal Medicine, University Hospital, Geneva, Switzerland. Fabrizio.montecucco@unige.ch
authors: Fabrizio
authors: F
authors: Montecucco
authors: Vincent
authors: V
authors: Braunersreuther
authors: Sébastien
authors: S
authors: Lenglet
authors: Benedicte M A
authors: BM
authors: Delattre
authors: Graziano
authors: G
authors: Pelli
authors: Vanessa
authors: V
authors: Buatois
authors: Florence
authors: F
authors: Guilhot
authors: Katia
authors: K
authors: Galan
authors: Nicolas
authors: N
authors: Vuilleumier
authors: Walter
authors: W
authors: Ferlin
authors: Nicolas
authors: N
authors: Fischer
authors: Jean-Paul
authors: JP
authors: Vallée
authors: Marie
authors: M
authors: Kosco-Vilbois
authors: François
authors: F
authors: Mach