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Regulation of thrombospondin-1 production by angiotensin II in rat heart endothelial cells

Authors
Journal
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research
0167-4889
Publisher
Elsevier
Publication Date
Volume
1357
Issue
2
Identifiers
DOI: 10.1016/s0167-4889(97)00029-3
Keywords
  • Angiotensin Ii
  • Thrombospondin-1
  • Heart Endothelial Cell
  • Protein Kinase C
  • (Rat)
Disciplines
  • Biology

Abstract

Abstract Thrombospondin-1 (TSP-1) is synthesized, secreted, and incorporated into the extracellular matrix by a variety of cells, including the endothelial cells. Addition of angiotensin II (AII) significantly induced TSP-1 mRNA in rat heart-derived endothelial cells. TSP-1 mRNA levels reached a plateau within 2 h after the addition of AII and decreased after 5 h. The induction was superinduced by cycloheximide and blocked by actinomycin D. Losartan, an AT1 receptor antagonist, could abolish the induction of TSP-1 mRNA by AII. Phorbol 12-myristate 13-acetate (TPA) was found to enhance TSP-1 mRNA level whereas a protein kinase C inhibitor, H7, was shown to block the induction. Immunoblot analysis revealed that TSP-1 was detectable in the medium 4 h after AII stimulation. Our results suggest that the upregulation of TSP-1 by AII represents an important mechanism leading to perivascular fibrosis in the heart.

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