Regulation of thrombospondin-1 production by angiotensin II in rat heart endothelial cells.
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.
Chua
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CC
Division of Geriatric Medicine, James Quillen School of Medicine, East Tennessee State University and Veterans Affairs Medical Center, Johnson City 37614, USA.
Hamdy
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RC
Chua
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BH
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D015152:Blotting, Northern; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D004727:Endothelium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects*; D007093:Imidazoles / Q000494:pharmacology; D019808:Losartan; D008562:Membrane Glycoproteins / Q000096:biosynthesis / Q000235:genetics*; D009206:Myocardium / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D013777:Tetrazoles / Q000494:pharmacology; D019699:Thrombospondins
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D007093:Imidazoles; D008562:Membrane Glycoproteins; D011725:Pyridines; D013777:Tetrazoles; D019699:Thrombospondins; D000804:Angiotensin II; C073402:PD 123319; D003609:Dactinomycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D003513:Cycloheximide; D011493:Protein Kinase C; D019808:Losartan