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

Ping Kong, Panagiota Christia, Amit Saxena, Ya Su, Nikolaos G. Frangogiannis

Research output: Contribution to journalArticle

99 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)H1363-H1372
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume305
Issue number9
DOIs
StatePublished - Nov 1 2013

Keywords

  • Cardiac fibrosis
  • Cardiac remodeling
  • Fibroblast
  • Myocardial infarction
  • Periostin

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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