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

• Published in: Thrombosis research Vol. 121; no. 1; pp. 59 - 65
• Main Authors: Pasten, Consuelo, Olave, Nelida C, Zhou, Lihua, Tabengwa, Edlue M, Wolkowicz, Paul E, Grenett, Hernan E
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Ltd 2007; Elsevier Science
• Subjects: Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Blood. Blood coagulation. Reticuloendothelial system; Cardiology. Vascular system; Cardiotonic Agents; Catechin - pharmacology; Cells, Cultured; Coronary Vessels - cytology; Diseases of the peripheral vessels. Diseases of the vena cava. Miscellaneous; Down-Regulation - genetics; Endothelial cell; Endothelial Cells - cytology; Endothelial Cells - metabolism; Endothelium, Vascular - cytology; Endothelium, Vascular - metabolism; Extracellular Signal-Regulated MAP Kinases - metabolism; Flavonoids - pharmacology; Fundamental and applied biological sciences. Psychology; Gene Expression Regulation; Hematology, Oncology and Palliative Medicine; Humans; JNK Mitogen-Activated Protein Kinases - metabolism; MAP Kinase Signaling System; Medical sciences; Pharmacology. Drug treatments; Phenols - pharmacology; Plasminogen Activator Inhibitor 1 - analysis; Plasminogen Activator Inhibitor 1 - genetics; Plasminogen activator inhibitor type-1; Polyphenols; Quercetin - pharmacology; Quercetin, catechin; Red wine polyphenols; Signal transduction pathway; Transcription, Genetic; Vertebrates: cardiovascular system; endothelial cells; Endothelial cell; HCAECs; DMSO; Tris-buffered saline containing 0.1% Tween 20; PAGE; Quercetin, catechin; MAPK; Red wine polyphenols; mitogen-activated protein kinase; Human coronary artery endothelial cells; plasminogen activator inhibitor type-1; TBS-T; dimethyl sulfoxide; ECs; PMSF; luciferase; PAI-1; polyacrylamide gel electrophoresis; phenylmethylsulfonylfluoride; luc; Signal transduction pathway; Plasminogen activator inhibitor type-1; Human; Cell culture; Catechin; Enzyme; Transferases; Non-specific serine/threonine protein kinase; Coronary artery; Cardiovascular disease; Endothelial cell; Plasminogen activator inhibitor type-1; Red wine polyphenols; Quercetin; Gene expression; Red wine; Flavonoid; Epidemiology; Polymerase chain reaction; Plasminogen activator inhibitor 1; Signal transduction; Polyphenol; Treatment; Quercetin; catechin; Signal transduction pathway; Phenols; Immunoblotting assay
• ISSN: 0049-3848; 1879-2472
• DOI: 10.1016/j.thromres.2007.02.001

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.