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Title: Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation

Abstract

Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferationmore » to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there was no modulation by E2 in either cell-type. In conclusion, TNF-{alpha} induced SV neointima formation, increased SMC proliferation and migration, impaired SV-EC migration and increased expression of adhesion molecules. E2 exerted distinct cell-type and function-specific modulation, the mechanisms underlying which are worthy of further detailed study.« less

Authors:
 [1];  [2];  [3]; ;  [1];  [2]; ; ;  [4];  [1];  [2];  [1];  [2]
  1. Division of Cardiovascular Medicine, Leeds Institute of Genetics, Health and Therapeutics, University of Leeds, Leeds LS2 9JT (United Kingdom)
  2. (MCRC), University of Leeds, Leeds LS2 9JT (United Kingdom)
  3. (Thailand)
  4. Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University (Thailand)
Publication Date:
OSTI Identifier:
22207821
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 420; Journal Issue: 4; Other Information: Copyright (c) 2012 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CARDIOVASCULAR DISEASES; CONCENTRATION RATIO; CORONARIES; ESTRADIOL; INCUBATION; LYMPHOKINES; MUSCLES; RADIOPROTECTIVE SUBSTANCES; REPAIR; VEINS

Citation Formats

Nintasen, Rungrat, Multidisciplinary Cardiovascular Research Center, Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Riches, Kirsten, Mughal, Romana S., Multidisciplinary Cardiovascular Research Center, Viriyavejakul, Parnpen, Chaisri, Urai, Maneerat, Yaowapa, Turner, Neil A., Multidisciplinary Cardiovascular Research Center, Porter, Karen E., E-mail: medkep@leeds.ac.uk, and Multidisciplinary Cardiovascular Research Center. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation. United States: N. p., 2012. Web. doi:10.1016/J.BBRC.2012.03.082.
Nintasen, Rungrat, Multidisciplinary Cardiovascular Research Center, Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Riches, Kirsten, Mughal, Romana S., Multidisciplinary Cardiovascular Research Center, Viriyavejakul, Parnpen, Chaisri, Urai, Maneerat, Yaowapa, Turner, Neil A., Multidisciplinary Cardiovascular Research Center, Porter, Karen E., E-mail: medkep@leeds.ac.uk, & Multidisciplinary Cardiovascular Research Center. Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation. United States. doi:10.1016/J.BBRC.2012.03.082.
Nintasen, Rungrat, Multidisciplinary Cardiovascular Research Center, Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University, Riches, Kirsten, Mughal, Romana S., Multidisciplinary Cardiovascular Research Center, Viriyavejakul, Parnpen, Chaisri, Urai, Maneerat, Yaowapa, Turner, Neil A., Multidisciplinary Cardiovascular Research Center, Porter, Karen E., E-mail: medkep@leeds.ac.uk, and Multidisciplinary Cardiovascular Research Center. Fri . "Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation". United States. doi:10.1016/J.BBRC.2012.03.082.
@article{osti_22207821,
title = {Divergent effects of 17-{beta}-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-{alpha}-induced neointima formation},
author = {Nintasen, Rungrat and Multidisciplinary Cardiovascular Research Center and Department of Tropical Pathology, Faculty of Tropical Medicine, Mahidol University and Riches, Kirsten and Mughal, Romana S. and Multidisciplinary Cardiovascular Research Center and Viriyavejakul, Parnpen and Chaisri, Urai and Maneerat, Yaowapa and Turner, Neil A. and Multidisciplinary Cardiovascular Research Center and Porter, Karen E., E-mail: medkep@leeds.ac.uk and Multidisciplinary Cardiovascular Research Center},
abstractNote = {Highlights: Black-Right-Pointing-Pointer TNF-{alpha} augments neointimal hyperplasia in human saphenous vein. Black-Right-Pointing-Pointer TNF-{alpha} induces detrimental effects on endothelial and smooth muscle cell function. Black-Right-Pointing-Pointer Estradiol exerts modulatory effects on TNF-induced vascular cell functions. Black-Right-Pointing-Pointer The modulatory effects of estradiol are discriminatory and cell-type specific. -- Abstract: Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-{alpha} (TNF-{alpha}). TNF-{alpha} can induce vascular endothelial cell (EC) and smooth muscle cell (SMC) dysfunction, central events in development of neointimal lesions. The reduced incidence of CHD in young women is believed to be due to the protective effects of estradiol (E2). We therefore investigated the effects of TNF-{alpha} on human neointima formation and SMC/EC functions and any modulatory effects of E2. Saphenous vein (SV) segments were cultured in the presence of TNF-{alpha} (10 ng/ml), E2 (2.5 nM) or both in combination. Neointimal thickening was augmented by incubation with TNF-{alpha}, an effect that was abolished by co-culture with E2. TNF-{alpha} increased SV-SMC proliferation in a concentration-dependent manner that was optimal at 10 ng/ml (1.5-fold increase), and abolished by E2 at all concentrations studied (1-50 nM). Surprisingly, E2 itself at low concentrations (1 and 5 nM) stimulated SV-SMC proliferation to a level comparable to that of TNF-{alpha} alone. SV-EC migration was significantly impaired by TNF-{alpha} (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-{alpha} increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-{alpha} potently induced ICAM-1 and VCAM-1 expression in both SV-EC and SV-SMC. However there was no modulation by E2 in either cell-type. In conclusion, TNF-{alpha} induced SV neointima formation, increased SMC proliferation and migration, impaired SV-EC migration and increased expression of adhesion molecules. E2 exerted distinct cell-type and function-specific modulation, the mechanisms underlying which are worthy of further detailed study.},
doi = {10.1016/J.BBRC.2012.03.082},
journal = {Biochemical and Biophysical Research Communications},
number = 4,
volume = 420,
place = {United States},
year = {Fri Apr 20 00:00:00 EDT 2012},
month = {Fri Apr 20 00:00:00 EDT 2012}
}