Fibroblast progenitor cells are recruited into the myocardium prior to the development of myocardial fibrosis

Summary Using an established model of myocardial hypertrophy and fibrosis after angiotensin II (AngII) infusion, our aim was to characterize the early cellular element involved in the development of myocardial fibrosis in detail. Male Lewis rats were infused with saline or AngII (0.7 mg/kg per day)...

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Bibliographic Details
Published in:International journal of experimental pathology 2012-04, Vol.93 (2), p.115-124
Main Authors: Sopel, Mryanda, Falkenham, Alec, Oxner, Adam, Ma, Irene, Lee, Timothy D.G., Légaré, Jean-Francois
Format: Article
Language:English
Subjects:
AC133 Antigen
Actins - metabolism
Angiotensin II - toxicity
Animals
Antigens, CD - metabolism
Biomarkers - metabolism
Cell Movement - drug effects
Cells, Cultured
Chemokine CCL2 - metabolism
Chemokines - metabolism
Collagen - metabolism
Disease Models, Animal
Ectodysplasins - metabolism
Extracellular Matrix - metabolism
Fibroblasts - drug effects
Fibroblasts - metabolism
Fibroblasts - pathology
fibrocytes
Fibrosis
Glycoproteins - metabolism
Heart - drug effects
heart failure
hypertension
Male
mesenchymal progenitor cells
Mesenchymal Stromal Cells - drug effects
Mesenchymal Stromal Cells - metabolism
Mesenchymal Stromal Cells - pathology
myocardial fibrosis
Myocardium - metabolism
Myocardium - pathology
Myocytes, Cardiac - drug effects
Myocytes, Cardiac - metabolism
Myocytes, Cardiac - pathology
Original
Peptides - metabolism
Rats
Rats, Inbred Lew
renin-angiotensin system
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Summary:Summary Using an established model of myocardial hypertrophy and fibrosis after angiotensin II (AngII) infusion, our aim was to characterize the early cellular element involved in the development of myocardial fibrosis in detail. Male Lewis rats were infused with saline or AngII (0.7 mg/kg per day) for up to seven days. Collagen deposition and cellular infiltration were identified by histology stains. Infiltrating cells were grown in vitro and examined by flow cytometry and immunostaining. Chemokine expression was measured using qRT‐PCR. AngII infusion resulted in multifocal myocardial cellular infiltration (peak at three days) that preceded collagen deposition. Monocyte chemotactic protein (MCP)‐1 transcripts peaked after one day of AngII exposure. Using a triple‐labelling technique, the infiltrating cells were found to express markers of leucocyte (ED1+), mesenchymal [α‐smooth muscle actin (SMA)+] and haematopeotic progenitor cells (CD133+) suggesting a fibroblast progenitor phenotype. In vitro, ED1+/SMA+/CD133+ cells were isolated and grown from AngII‐exposed animals. Comparatively few cells were cultured from untreated control hearts, and they were found to be ED1−/SMA+/CD133−. We provide evidence that myocardial ECM deposition is preceded by infiltration into the myocardium by cells that express a combination of haematopoietic (ED1, CD133) and mesenchymal (SMA) cell markers, which is a characteristic of the phenotype of fibroblast precursor cells, termed fibrocytes. This suggests that fibrocytes rather than (as is often presumed) leucocytes may have effector functions in the initiation of myocardial fibrosis.
ISSN:0959-9673
1365-2613
DOI:10.1111/j.1365-2613.2011.00797.x