Polyphenols downregulate PAI-1 gene expression in cultured human coronary artery endothelial cells: Molecular contributor to cardiovascular protection

Consuelo Pasten, Nelida C. Olave, Lihua Zhou, Edlue M. Tabengwa, Paul E. Wolkowicz, Hernan E. Grenett

Research output: Contribution to journalArticlepeer-review

36 Scopus citations

Abstract

Epidemiologic data have indicated that the intake of polyphenols is inversely associated with mortality from cardiovascular disease. Mitogen-activated protein kinases (MAPKs) are ubiquitous signaling proteins that have been associated with gene regulation. This study determined whether polyphenols (catechin and quercetin) activated kinase-signaling cascades that suppress PAI-1 expression and whether this suppression is at the transcription level in human coronary artery endothelial cells (ECs) remains unresolved. ECs were incubated in the absence/presence of polyphenols and RNA and protein were analyzed by real-time PCR and Western blot analysis. MAPKs were analyzed using antibodies to active form of p38, JNK, and ERK1/2. ECs were transiently transfected with a 1.1-kb PAI-1 promoter (pPAI110/luc) and promoter activity were assays after treatment with polyphenols. Catechin and quercetin decreased EC PAI-1 mRNA in a time- and dose-dependent manner, reaching a maximum at 4 and 2 h, respectively. These polyphenols activated EC p38 and ERK1/2 within 2.5 and 5 min, respectively, while maximal JNK activation occurred at 10-15 min. An inhibitor of p38 MAPK had no effect on polyphenol-induced repression of PAI-1. Inhibitors of ERK or JNK prevented polyphenol repression of EC PAI-1 gene expression. Exposing ECs transiently transfected with pPAI110/luc to polyphenols decreased promoter activity 50%. Polyphenols repress EC PAI-1 expression, in part, by activating ERK and JNK signaling pathways and this repression is at transcriptional levels. Thus MAPK seem to play an important role in polyphenol-induce repression of PAI-1 expression in ECs.

Original languageEnglish
Pages (from-to)59-65
Number of pages7
JournalThrombosis Research
Volume121
Issue number1
DOIs
StatePublished - 2007
Externally publishedYes

Bibliographical note

Funding Information:
These studies were supported by National Institutes of Heath grant PO1 HL70610, Project 2.

Keywords

  • Endothelial cell
  • Plasminogen activator inhibitor type-1
  • Quercetin, catechin
  • Red wine polyphenols
  • Signal transduction pathway

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