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Am J Physiol Heart Circ Physiol. 2013 Nov 1;305(9):H1363-72. doi: 10.1152/ajpheart.00395.2013. Epub 2013 Aug 30.

Lack of specificity of fibroblast-specific protein 1 in cardiac remodeling and fibrosis.

Author information

1
Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology Albert Einstein College of Medicine, Bronx, New York.

Abstract

Understanding the role of fibroblasts in pathologic conditions is hampered by the absence of specific markers. Fibroblast-specific protein (FSP)1 has been suggested as a fibroblast-specific marker in normal and fibrotic tissues; FSP1 reporter mice and FSP1-Cre-driven gene deletion are considered reliable strategies to investigate fibroblast biology. Because fibroblasts are abundant in normal and injured mammalian hearts, we studied the identity of FSP1(+) cells in the infarcted and remodeling myocardium using mice with green fluorescent protein (GFP) expression driven by the FSP1 promoter. Neonatal and adult mouse hearts had low numbers of FSP1(+) cells. Myocardial infarction induced marked infiltration with FSP1-expressing cells that peaked after 72 h of reperfusion. Using flow cytometry, we identified 50% of FSP1(+) cells as hematopoietic cells; many endothelial cells were also FSP1(+). Increased infiltration with FSP1(+) cells was also noted in the pressure-overloaded myocardium. Although some FSP1(+) cells had fibroblast morphology, >30% were identified as hematopoietic cells, endothelial cells, or vascular smooth muscle cells. In contrast, periostin did not stain leukocytes or vascular cells but labeled spindle-shaped interstitial cells and, as a typical matricellular protein, was deposited in the matrix. CD11b(+) myeloid cells sorted from the infarcted heart had higher FSP1 expression than corresponding CD11b-negative cells, highlighting the predominant expression by hematopoietic cells. FSP1 is not a specific marker for fibroblasts in cardiac remodeling and fibrosis.

KEYWORDS:

cardiac fibrosis; cardiac remodeling; fibroblast; myocardial infarction; periostin

PMID:
23997102
PMCID:
PMC3840245
DOI:
10.1152/ajpheart.00395.2013
[Indexed for MEDLINE]
Free PMC Article

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