Title

Inhibition Of Plasminogen Activator Inhibitor-1 Expression In Vascular Smooth Muscle Cells By Protoporphyrins Through A Heme Oxygenase-Independent Mechanism

Keywords

Heme oxygenase; Plasminogen activator inhibitor-1; Protoporphyrin; TGFβ1; Vascular smooth muscle cells

Abstract

Heme oxygenase-1 (HO-1), a rate-limiting enzyme in heme catabolism, has been shown to play a regulatory role in the expression of plasminogen activator inhibitor-1 (PAI-1), a risk factor for vascular disease. Accordingly, we examined the effect of protoporphyrins, both HO inhibitors and activators, on PAI-1 expression in human vascular smooth muscle cells (VSMCs). Tin-protoporphyrin (SnPP) markedly inhibited the transforming growth factor β1 (TGFβ1)-induced expression of PAI-1 protein. Protoporphyrins, whether they are inhibitors or activators of HO, produced a similar inhibitory effect. However, SnPP had no effect on the level of PAI-1 mRNA transcripts. Knockdown of human HO-1 with a specific siRNA did not reduce the PAI-1 protein level in TGFβ1-treated cells. In addition, the proteasome inhibitor lactacystin reversed the inhibitory effect of SnPP on PAI-1 protein expression. Both cobalt-protoporphyrin (CoPP) and CoCl2 markedly induced HO-1 expression. However, CoPP did not affect PAI-1 gene expression, whereas CoCl2 upregulated PAI-1 mRNA in a dose-dependent manner. Our results demonstrate that protoporphyrins can block the TGFβ1-mediated induction of PAI-1 protein in VSMCs and that this inhibitory effect is independent of HO activity. © Springer Science+Business Media, LLC. 2008.

Publication Date

5-1-2008

Publication Title

Molecular and Cellular Biochemistry

Volume

312

Issue

1-2

Number of Pages

93-101

Document Type

Article

Personal Identifier

scopus

DOI Link

https://doi.org/10.1007/s11010-008-9724-6

Socpus ID

42149146253 (Scopus)

Source API URL

https://api.elsevier.com/content/abstract/scopus_id/42149146253

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