Mast cell tryptase may modulate endothelial cell phenotype in healing myocardial infarcts

Porur Somasundaram, Guofeng Ren, Himanshu Nagar, Daniela Kraemer, Leonardo Mendoza, Lloyd H. Michael, George H. Caughey, Mark L. Entman, Nikolaos G. Frangogiannis

Research output: Contribution to journalArticlepeer-review

81 Scopus citations


Mast cells and macrophages infiltrate healing myocardial infarcts and may play an important role in regulating fibrous tissue deposition and extracellular matrix remodelling. This study examined the time-course of macrophage and mast cell accumulation in healing infarcts and studied the histological characteristics and protease expression profile of mast cells in a canine model of experimental infarction. Although macrophages were more numerous than mast cells in infarct granulation tissue, macrophage density decreased during maturation of the scar, whereas mast cell numbers remained persistently elevated. During the inflammatory phase of infarction, newly recruited leucocytes infiltrated the injured myocardium and appeared to be clustered in close proximity to degranulating cardiac mast cells. During the proliferative phase of healing, mast cells had decreased granular content and were localized close to infarct neovessels. In contrast, macrophages showed no selective localization. Mast cells in healing canine infarcts were alcian blue/safranin-positive cells that expressed both tryptase and chymase. In order to explain the pro-inflammatory and angiogenic actions of tryptase - the major secretory protein of mast cells - its effects on endothelial chemokine expression were examined. Chemokines are chemotactic cytokines that play an important role in leucocyte trafficking and angiogenesis and are highly induced in infarcts. Tryptase, a proteinase-activated receptor (PAR)-2 agonist, induced endothelial expression of the angiogenic chemokines CCL2/MCP-1 and CXCL8/IL-8, but not the angiostatic chemokine CXCL10/IP-10. Endothelial PAR-2 stimulation with the agonist peptide SLIGKV induced a similar chemokine expression profile. Mast cell tryptase may exert its angiogenic effects in part through selective stimulation of angiogenic chemokines.

Original languageEnglish (US)
Pages (from-to)102-111
Number of pages10
JournalJournal of Pathology
Issue number1
StatePublished - Jan 2005
Externally publishedYes


  • Chemokine
  • Chymase
  • Infarction
  • Inflammation
  • Macrophage
  • Mast cell
  • Myocardial ischaemia/reperfusion
  • Tryptase

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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