The soybean isoflavonoid equol blocks ritonavir-induced endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells

Charlie Cheng, Xinwen Wang, Sarah M. Weakley, Panagiotis Kougias, Peter H. Lin, Qizhi Yao, Changyi Chen

Research output: Contribution to journalArticle

19 Citations (Scopus)

Abstract

HIV protease inhibitor (PI) ritonavir (RTV) may cause vascular injury through oxidative stress. Our purpose in this study was to determine whether equol, a soy isoflavone, could prevent RTV-induced endothelial dysfunction in porcine pulmonary arteries and in human pulmonary artery endothelial cells (HPAEC). Fresh porcine pulmonary artery rings were treated with 15 mmol/L of RTV and/or equol in concentrations of 0.1, 1, and 10 μmol/L for 24 h. A control was set with no amount of equol or RTV administered. Based on myograph tension analysis, RTV significantly reduced endothelium-dependent relaxation in response to bradykinin in the artery rings compared with untreated vessels, whereas the antioxidant equol effectively reversed the RTV effect in a concentration- dependent manner. RTV also reduced the contraction of artery rings in response to thromboxane A(2) analogue U46619 and this reduction was blocked by equol. In addition, RTV treatment significantly reduced endothelial nitric oxide synthase (eNOS) expression in both porcine pulmonary arteries and HPAEC, whereas equol effectively blocked RTV-induced eNOS downregulation. Furthermore, RTV significantly increased superoxide anion production, whereas equol reversed this effect of RTV in porcine pulmonary arteries. Thus, the antioxidant equol effectively protects vascular function from the detrimental effects of HIV PI RTV in both porcine pulmonary arteries and HPAEC via a reduction in the vasomotor dysfunction, eNOS downregulation, and oxidative stress induced by RTV. These novel data suggest that equol may have a clinical application in preventing HIV-associated cardiovascular complications.

Original languageEnglish
Pages (from-to)12-17
Number of pages6
JournalJournal of Nutrition
Volume140
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

Fingerprint

Equol
Ritonavir
Soybeans
Pulmonary Artery
Swine
Endothelial Cells
Nitric Oxide Synthase Type III
HIV Protease Inhibitors
Oxidative Stress
Down-Regulation
Arteries
Antioxidants
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Isoflavones
Vascular System Injuries
Thromboxanes
Bradykinin

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Nutrition and Dietetics

Cite this

The soybean isoflavonoid equol blocks ritonavir-induced endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells. / Cheng, Charlie; Wang, Xinwen; Weakley, Sarah M.; Kougias, Panagiotis; Lin, Peter H.; Yao, Qizhi; Chen, Changyi.

In: Journal of Nutrition, Vol. 140, No. 1, 01.2010, p. 12-17.

Research output: Contribution to journalArticle

Cheng, Charlie ; Wang, Xinwen ; Weakley, Sarah M. ; Kougias, Panagiotis ; Lin, Peter H. ; Yao, Qizhi ; Chen, Changyi. / The soybean isoflavonoid equol blocks ritonavir-induced endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells. In: Journal of Nutrition. 2010 ; Vol. 140, No. 1. pp. 12-17.
@article{1880f76a039e4b6ea56e6d666d6fa247,
title = "The soybean isoflavonoid equol blocks ritonavir-induced endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells",
abstract = "HIV protease inhibitor (PI) ritonavir (RTV) may cause vascular injury through oxidative stress. Our purpose in this study was to determine whether equol, a soy isoflavone, could prevent RTV-induced endothelial dysfunction in porcine pulmonary arteries and in human pulmonary artery endothelial cells (HPAEC). Fresh porcine pulmonary artery rings were treated with 15 mmol/L of RTV and/or equol in concentrations of 0.1, 1, and 10 μmol/L for 24 h. A control was set with no amount of equol or RTV administered. Based on myograph tension analysis, RTV significantly reduced endothelium-dependent relaxation in response to bradykinin in the artery rings compared with untreated vessels, whereas the antioxidant equol effectively reversed the RTV effect in a concentration- dependent manner. RTV also reduced the contraction of artery rings in response to thromboxane A(2) analogue U46619 and this reduction was blocked by equol. In addition, RTV treatment significantly reduced endothelial nitric oxide synthase (eNOS) expression in both porcine pulmonary arteries and HPAEC, whereas equol effectively blocked RTV-induced eNOS downregulation. Furthermore, RTV significantly increased superoxide anion production, whereas equol reversed this effect of RTV in porcine pulmonary arteries. Thus, the antioxidant equol effectively protects vascular function from the detrimental effects of HIV PI RTV in both porcine pulmonary arteries and HPAEC via a reduction in the vasomotor dysfunction, eNOS downregulation, and oxidative stress induced by RTV. These novel data suggest that equol may have a clinical application in preventing HIV-associated cardiovascular complications.",
author = "Charlie Cheng and Xinwen Wang and Weakley, {Sarah M.} and Panagiotis Kougias and Lin, {Peter H.} and Qizhi Yao and Changyi Chen",
year = "2010",
month = "1",
doi = "10.3945/jn.109.110981",
language = "English",
volume = "140",
pages = "12--17",
journal = "Journal of Nutrition",
issn = "0022-3166",
publisher = "American Society for Nutrition",
number = "1",

}

TY - JOUR

T1 - The soybean isoflavonoid equol blocks ritonavir-induced endothelial dysfunction in porcine pulmonary arteries and human pulmonary artery endothelial cells

AU - Cheng, Charlie

AU - Wang, Xinwen

AU - Weakley, Sarah M.

AU - Kougias, Panagiotis

AU - Lin, Peter H.

AU - Yao, Qizhi

AU - Chen, Changyi

PY - 2010/1

Y1 - 2010/1

N2 - HIV protease inhibitor (PI) ritonavir (RTV) may cause vascular injury through oxidative stress. Our purpose in this study was to determine whether equol, a soy isoflavone, could prevent RTV-induced endothelial dysfunction in porcine pulmonary arteries and in human pulmonary artery endothelial cells (HPAEC). Fresh porcine pulmonary artery rings were treated with 15 mmol/L of RTV and/or equol in concentrations of 0.1, 1, and 10 μmol/L for 24 h. A control was set with no amount of equol or RTV administered. Based on myograph tension analysis, RTV significantly reduced endothelium-dependent relaxation in response to bradykinin in the artery rings compared with untreated vessels, whereas the antioxidant equol effectively reversed the RTV effect in a concentration- dependent manner. RTV also reduced the contraction of artery rings in response to thromboxane A(2) analogue U46619 and this reduction was blocked by equol. In addition, RTV treatment significantly reduced endothelial nitric oxide synthase (eNOS) expression in both porcine pulmonary arteries and HPAEC, whereas equol effectively blocked RTV-induced eNOS downregulation. Furthermore, RTV significantly increased superoxide anion production, whereas equol reversed this effect of RTV in porcine pulmonary arteries. Thus, the antioxidant equol effectively protects vascular function from the detrimental effects of HIV PI RTV in both porcine pulmonary arteries and HPAEC via a reduction in the vasomotor dysfunction, eNOS downregulation, and oxidative stress induced by RTV. These novel data suggest that equol may have a clinical application in preventing HIV-associated cardiovascular complications.

AB - HIV protease inhibitor (PI) ritonavir (RTV) may cause vascular injury through oxidative stress. Our purpose in this study was to determine whether equol, a soy isoflavone, could prevent RTV-induced endothelial dysfunction in porcine pulmonary arteries and in human pulmonary artery endothelial cells (HPAEC). Fresh porcine pulmonary artery rings were treated with 15 mmol/L of RTV and/or equol in concentrations of 0.1, 1, and 10 μmol/L for 24 h. A control was set with no amount of equol or RTV administered. Based on myograph tension analysis, RTV significantly reduced endothelium-dependent relaxation in response to bradykinin in the artery rings compared with untreated vessels, whereas the antioxidant equol effectively reversed the RTV effect in a concentration- dependent manner. RTV also reduced the contraction of artery rings in response to thromboxane A(2) analogue U46619 and this reduction was blocked by equol. In addition, RTV treatment significantly reduced endothelial nitric oxide synthase (eNOS) expression in both porcine pulmonary arteries and HPAEC, whereas equol effectively blocked RTV-induced eNOS downregulation. Furthermore, RTV significantly increased superoxide anion production, whereas equol reversed this effect of RTV in porcine pulmonary arteries. Thus, the antioxidant equol effectively protects vascular function from the detrimental effects of HIV PI RTV in both porcine pulmonary arteries and HPAEC via a reduction in the vasomotor dysfunction, eNOS downregulation, and oxidative stress induced by RTV. These novel data suggest that equol may have a clinical application in preventing HIV-associated cardiovascular complications.

UR - http://www.scopus.com/inward/record.url?scp=73649112372&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=73649112372&partnerID=8YFLogxK

U2 - 10.3945/jn.109.110981

DO - 10.3945/jn.109.110981

M3 - Article

VL - 140

SP - 12

EP - 17

JO - Journal of Nutrition

JF - Journal of Nutrition

SN - 0022-3166

IS - 1

ER -