Divergent effects of 17-β-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-α-induced neointima formation

Rungrat Nintasen, Kirsten Riches, Romana S. Mughal, Parnpen Viriyavejakul, Urai Chaisri, Yaowapa Maneerat, Neil A. Turner, Karen E. Porter

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α). TNF-α 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-α 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-α (10. ng/ml), E2 (2.5. nM) or both in combination.Neointimal thickening was augmented by incubation with TNF-α, an effect that was abolished by co-culture with E2. TNF-α 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-α alone. SV-EC migration was significantly impaired by TNF-α (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-α increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-α 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-α 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.

Original languageEnglish
Pages (from-to)828-833
Number of pages6
JournalBiochemical and Biophysical Research Communications
Volume420
Issue number4
DOIs
Publication statusPublished - 20 Apr 2012
Externally publishedYes

Fingerprint

Neointima
Endothelial cells
Saphenous Vein
Vascular Smooth Muscle
Smooth Muscle Myocytes
Muscle
Estradiol
Endothelial Cells
Tumor Necrosis Factor-alpha
Cell Movement
Cell proliferation
Cell Proliferation
Coculture Techniques
Coronary Disease
Modulation
Vascular Cell Adhesion Molecule-1
Intercellular Adhesion Molecule-1
Cell culture
Repair
Adhesion

Cite this

Nintasen, Rungrat ; Riches, Kirsten ; Mughal, Romana S. ; Viriyavejakul, Parnpen ; Chaisri, Urai ; Maneerat, Yaowapa ; Turner, Neil A. ; Porter, Karen E. / Divergent effects of 17-β-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-α-induced neointima formation. In: Biochemical and Biophysical Research Communications. 2012 ; Vol. 420, No. 4. pp. 828-833.
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abstract = "Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α). TNF-α 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-α 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-α (10. ng/ml), E2 (2.5. nM) or both in combination.Neointimal thickening was augmented by incubation with TNF-α, an effect that was abolished by co-culture with E2. TNF-α 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-α alone. SV-EC migration was significantly impaired by TNF-α (42{\%} of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-α increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-α 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-α 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.",
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Divergent effects of 17-β-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-α-induced neointima formation. / Nintasen, Rungrat; Riches, Kirsten; Mughal, Romana S.; Viriyavejakul, Parnpen; Chaisri, Urai; Maneerat, Yaowapa; Turner, Neil A.; Porter, Karen E.

In: Biochemical and Biophysical Research Communications, Vol. 420, No. 4, 20.04.2012, p. 828-833.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Divergent effects of 17-β-estradiol on human vascular smooth muscle and endothelial cell function diminishes TNF-α-induced neointima formation

AU - Nintasen, Rungrat

AU - Riches, Kirsten

AU - Mughal, Romana S.

AU - Viriyavejakul, Parnpen

AU - Chaisri, Urai

AU - Maneerat, Yaowapa

AU - Turner, Neil A.

AU - Porter, Karen E.

PY - 2012/4/20

Y1 - 2012/4/20

N2 - Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α). TNF-α 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-α 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-α (10. ng/ml), E2 (2.5. nM) or both in combination.Neointimal thickening was augmented by incubation with TNF-α, an effect that was abolished by co-culture with E2. TNF-α 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-α alone. SV-EC migration was significantly impaired by TNF-α (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-α increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-α 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-α 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.

AB - Coronary heart disease (CHD) is a condition characterized by increased levels of proinflammatory cytokines, including tumor necrosis factor-α (TNF-α). TNF-α 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-α 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-α (10. ng/ml), E2 (2.5. nM) or both in combination.Neointimal thickening was augmented by incubation with TNF-α, an effect that was abolished by co-culture with E2. TNF-α 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-α alone. SV-EC migration was significantly impaired by TNF-α (42% of control), and co-culture with E2 partially restored the ability of SV-EC to migrate and repair the wound. In contrast, TNF-α increased SV-SMC migration by 1.7-fold, an effect that was completely reversed by co-incubation with E2. Finally, TNF-α 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-α 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.

KW - 17-β-estradiol

KW - Endothelial cell

KW - Human

KW - Neointima

KW - Smooth muscle cell

KW - TNF-α

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U2 - 10.1016/j.bbrc.2012.03.082

DO - 10.1016/j.bbrc.2012.03.082

M3 - Article

VL - 420

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EP - 833

JO - Biochemical and Biophysical Research Communications

JF - Biochemical and Biophysical Research Communications

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