title: Non-human primate and rat cardiac fibroblasts show similar extracellular matrix-related and cellular adhesion gene responses to substance P.
abstract: BACKGROUND
  The sensory nerve neuropeptide substance P (SP) regulates cardiac fibrosis in rodents under pressure overload conditions. Interestingly, SP induces transient increased expression of specific genes in isolated rat cardiac fibroblasts, without resultant changes in cell function. This suggests that SP 'primes' fibroblasts, but does not directly activate them. We investigated whether these unusual findings are specific to rodent fibroblasts or are translatable to a larger animal model more closely related to humans.
  
  
  METHODS
  We compared the effects of SP on genes associated with extracellular matrix (ECM) regulation, cell-cell adhesion, cell-matrix adhesion and ECM in cardiac fibroblasts isolated from a non-human primate and Sprague-Dawley rats.
  
  
  RESULTS
  We found that rodent and non-human primate cardiac fibroblasts showed similar responses in genes that relate to ECM regulation and cell adhesion in response to SP. There were large discrepancies in ECM component genes, however, this did not result in collagen or laminin synthesis in rat or non-human primate fibroblasts in response to SP.
  
  
  CONCLUSIONS
  This study further supports the notion that SP serves as a 'primer' for fibroblasts rather than initiating direct effects and suggests that rodent fibroblasts are a suitable model for studying gene and functional responses to SP in the absence of human or non-human primate fibroblasts.
authors.affiliation: Department of Internal Medicine, Section on Cardiology, Wake Forest School of Medicine, Winston-Salem, NC; Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Giselle C
authors.initials: GC
authors.lastname: Meléndez
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Manteufel
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI.
authors.forename: Heather M
authors.initials: HM
authors.lastname: Dehlin
authors.affiliation: Department of Pathology, Section on Comparative Medicine, Wake Forest School of Medicine, Winston-Salem, NC.
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Register
authors.affiliation: Department of Pharmacology and Toxicology, Medical College of Wisconsin, Milwaukee, WI; Cardiovascular Center, Medical College of Wisconsin, Milwaukee, WI. Electronic address: slevick@mcw.edu.
authors.forename: Scott P
authors.initials: SP
authors.lastname: Levick
mesh_terms: D000818:Animals; D002448:Cell Adhesion / Q000187:drug effects; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D008252:Macaca fascicularis; D008297:Male; D009206:Myocardium / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D013373:Substance P
keywords: Cardiac fibroblast; Collagen; Genes; Neuropeptide; Non-human primate