Epigallocatechin gallate attenuates proliferation and oxidative stress in human vascular smooth muscle cells induced by interleukin-1β via heme oxygenase-1.
Proliferation of vascular smooth muscle cells (VSMCs) triggered by inflammatory stimuli and oxidative stress contributes importantly to atherogenesis. The association of green tea consumption with cardiovascular protection has been well documented in epidemiological observations, however, the underlying mechanisms remain unclear. This study aimed to elucidate the effects of the most active green tea catechin derivative, (-)-epigallocatechin-3-gallate (EGCG), in human aortic smooth muscle cells (HASMCs), focusing particularly on the role of a potent anti-inflammatory and antioxidative enzyme heme oxygenase-1 (HO-1). We found that pretreatment of EGCG dose- and time-dependently induced HO-1 protein levels in HASMCs. EGCG inhibited interleukin- (IL-)1β-induced HASMC proliferation and oxidative stress in a dose-dependent manner. The HO-1 inducer CoPPIX decreased IL-1β-induced cell proliferation, whereas the HO-1 enzyme inhibitor ZnPPIX significantly reversed EGCG-caused growth inhibition in IL-1β-treated HASMCs. At the molecular level, EGCG treatment significantly activated nuclear factor erythroid-2-related factor (Nrf2) transcription activities. These results suggest that EGCG might serve as a complementary and alternative medicine in the treatment of these pathologies by inducing HO-1 expression and subsequently decreasing VSMC proliferation.
Department of Respiratory Therapy, College of Medicine, and Department of Medical Research, Translational Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Po-Len
PL
Liu
School of Medicine, College of Medicine, Chung Shan Medical University, Taichung 402, Taiwan ; Department of Neurosurgery, Chung Shan Medical University Hospital, Taichung 402, Taiwan.
Jung-Tung
0000-0002-5865-6753
JT
Liu
Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 801, Taiwan.
Hsuan-Fu
HF
Kuo
Department of Respiratory Therapy, College of Medicine, and Department of Medical Research, Translational Research Center, Kaohsiung Medical University, Kaohsiung 807, Taiwan ; Department of Internal Medicine, Department of Chest Surgery, Division of Cardiovascular Surgery and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Inn-Wen
0000-0001-8328-8684
IW
Chong
Department of Internal Medicine, Department of Chest Surgery, Division of Cardiovascular Surgery and Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung 807, Taiwan.
Chong-Chao
CC
Hsieh
D000975:Antioxidants / Q000494:pharmacology; D050197:Atherosclerosis / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004790:Enzyme Induction / Q000187:drug effects; D051547:Heme Oxygenase-1 / Q000096:biosynthesis*; D006801:Humans; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects
D000975:Antioxidants; D053583:Interleukin-1beta; D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D002392:Catechin; C045651:epigallocatechin gallate; D051547:Heme Oxygenase-1