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Thrombospondin‐1 in Pulmonary Artery Smooth Muscle Cell Growth Inhibition
Author(s) -
Hasak Stephen Lawler,
Ochoa Cristhiaan D,
Quinn Deborah A,
Hales Charles
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1435
Subject(s) - cardiology , medicine , thrombospondin 1 , pulmonary artery , thrombospondin , chemistry , angiogenesis , metalloproteinase , matrix metalloproteinase
Background: We have found that under normoxic conditions, conditioned media from pulmonary artery endothelial cells (PAEC) exposed to cyclic stretch inhibits pulmonary artery smooth muscle cell (PASMC) growth. Using a targeted proteomics approach we found that the secreted proteome of physiologically stressed PAECs changes dramatically after cyclic stretch. One of the peptides identified was Thrombospondin‐1 (TSP‐1), a matricellular protein with antiangiogenic properties. We hypothesize that TSP‐1 is responsible, at least in part, for the stretched PAEC inhibition of PASMC growth. Methods and Results: We confirmed that TSP‐1 was upregulated by stretch using ELISA. Human lyophilized TSP‐1 inhibited growth of both static and stretched human PASMC in a dose dependent manner. Using an antibody that blocked TSP‐1 binding to its receptor, CD36, the stretched PAEC induced inhibition of PASMC growth was blocked. Conclusions: TSP‐1, by binding to CD36 on PASMC, is responsible, at least in part, for PAEC induced PASMC growth inhibition. An in depth look at the mechanism by which TSP‐1 inhibits PASMC growth will lead to insights about the possible use of TSP‐1 as a therapy for Pulmonary Arterial Hypertension.