title: Lack of specificity of fibroblast-specific protein 1 in cardiac remodeling and fibrosis.
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.
authors.affiliation: Wilf Family Cardiovascular Research Institute, Department of Medicine (Cardiology Albert Einstein College of Medicine, Bronx, New York.
authors.forename: Ping
authors.initials: P
authors.lastname: Kong
authors.forename: Panagiota
authors.initials: P
authors.lastname: Christia
authors.forename: Amit
authors.initials: A
authors.lastname: Saxena
authors.forename: Ya
authors.initials: Y
authors.lastname: Su
authors.forename: Nikolaos G
authors.initials: NG
authors.lastname: Frangogiannis
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D039481:CD11b Antigen / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism* / Q000473:pathology; D005355:Fibrosis; D017930:Genes, Reporter; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D011401:Promoter Regions, Genetic; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D020257:Ventricular Remodeling
chemical_list: D015415:Biomarkers; D039481:CD11b Antigen; D015815:Cell Adhesion Molecules; C082838:Postn protein, mouse; D000071999:S100 Calcium-Binding Protein A4; D009418:S100 Proteins; C470944:S100a4 protein, mouse; D049452:Green Fluorescent Proteins
keywords: cardiac fibrosis; cardiac remodeling; fibroblast; myocardial infarction; periostin