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Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL

BACKGROUND: Increased levels of the most electronegative type of LDL, L5, have been observed in the plasma of patients with metabolic syndrome (MetS) and ST-segment elevation myocardial infarction and can induce endothelial dysfunction. Because men have a higher predisposition to developing coronary...

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Autores principales: Lee, An-Sheng, Chen, Wei-Yu, Chan, Hua-Chen, Hsu, Jing-Fang, Shen, Ming-Yi, Chang, Chia-Ming, Bair, Henry, Su, Ming-Jai, Chang, Kuan-Cheng, Chen, Chu-Huang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974745/
https://www.ncbi.nlm.nih.gov/pubmed/24666525
http://dx.doi.org/10.1186/1475-2840-13-64
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author Lee, An-Sheng
Chen, Wei-Yu
Chan, Hua-Chen
Hsu, Jing-Fang
Shen, Ming-Yi
Chang, Chia-Ming
Bair, Henry
Su, Ming-Jai
Chang, Kuan-Cheng
Chen, Chu-Huang
author_facet Lee, An-Sheng
Chen, Wei-Yu
Chan, Hua-Chen
Hsu, Jing-Fang
Shen, Ming-Yi
Chang, Chia-Ming
Bair, Henry
Su, Ming-Jai
Chang, Kuan-Cheng
Chen, Chu-Huang
author_sort Lee, An-Sheng
collection PubMed
description BACKGROUND: Increased levels of the most electronegative type of LDL, L5, have been observed in the plasma of patients with metabolic syndrome (MetS) and ST-segment elevation myocardial infarction and can induce endothelial dysfunction. Because men have a higher predisposition to developing coronary artery disease than do premenopausal women, we hypothesized that LDL electronegativity is increased in men and promotes endothelial damage. METHODS: L5 levels were compared between middle-aged men and age-matched, premenopausal women with or without MetS. We further studied the effects of gender-influenced LDL electronegativity on aortic cellular senescence and DNA damage in leptin receptor–deficient (db/db) mice by using senescence-associated–β-galactosidase and γH2AX staining, respectively. We also studied the protective effects of 17β-estradiol and genistein against electronegative LDL–induced senescence in cultured bovine aortic endothelial cells (BAECs). RESULTS: L5 levels were higher in MetS patients than in healthy subjects (P < 0.001), particularly in men (P = 0.001). LDL isolated from male db/db mice was more electronegative than that from male or female wild-type mice. In addition, LDL from male db/db mice contained abundantly more apolipoprotein CIII and induced more BAEC senescence than did female db/db or wild-type LDL. In the aortas of db/db mice but not wild-type mice, we observed cellular senescence and DNA damage, and the effect was more significant in male than in female db/db mice. Pretreatment with 17β-estradiol or genistein inhibited BAEC senescence induced by male or female db/db LDL and downregulated the expression of lectin-like oxidized LDL receptor-1 and tumor necrosis factor-alpha protein. CONCLUSION: The gender dichotomy of LDL-induced cardiovascular damage may underlie the increased propensity to coronary artery disease in men.
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spelling pubmed-39747452014-04-04 Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL Lee, An-Sheng Chen, Wei-Yu Chan, Hua-Chen Hsu, Jing-Fang Shen, Ming-Yi Chang, Chia-Ming Bair, Henry Su, Ming-Jai Chang, Kuan-Cheng Chen, Chu-Huang Cardiovasc Diabetol Original Investigation BACKGROUND: Increased levels of the most electronegative type of LDL, L5, have been observed in the plasma of patients with metabolic syndrome (MetS) and ST-segment elevation myocardial infarction and can induce endothelial dysfunction. Because men have a higher predisposition to developing coronary artery disease than do premenopausal women, we hypothesized that LDL electronegativity is increased in men and promotes endothelial damage. METHODS: L5 levels were compared between middle-aged men and age-matched, premenopausal women with or without MetS. We further studied the effects of gender-influenced LDL electronegativity on aortic cellular senescence and DNA damage in leptin receptor–deficient (db/db) mice by using senescence-associated–β-galactosidase and γH2AX staining, respectively. We also studied the protective effects of 17β-estradiol and genistein against electronegative LDL–induced senescence in cultured bovine aortic endothelial cells (BAECs). RESULTS: L5 levels were higher in MetS patients than in healthy subjects (P < 0.001), particularly in men (P = 0.001). LDL isolated from male db/db mice was more electronegative than that from male or female wild-type mice. In addition, LDL from male db/db mice contained abundantly more apolipoprotein CIII and induced more BAEC senescence than did female db/db or wild-type LDL. In the aortas of db/db mice but not wild-type mice, we observed cellular senescence and DNA damage, and the effect was more significant in male than in female db/db mice. Pretreatment with 17β-estradiol or genistein inhibited BAEC senescence induced by male or female db/db LDL and downregulated the expression of lectin-like oxidized LDL receptor-1 and tumor necrosis factor-alpha protein. CONCLUSION: The gender dichotomy of LDL-induced cardiovascular damage may underlie the increased propensity to coronary artery disease in men. BioMed Central 2014-03-25 /pmc/articles/PMC3974745/ /pubmed/24666525 http://dx.doi.org/10.1186/1475-2840-13-64 Text en Copyright © 2014 Lee et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/4.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Original Investigation
Lee, An-Sheng
Chen, Wei-Yu
Chan, Hua-Chen
Hsu, Jing-Fang
Shen, Ming-Yi
Chang, Chia-Ming
Bair, Henry
Su, Ming-Jai
Chang, Kuan-Cheng
Chen, Chu-Huang
Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL
title Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL
title_full Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL
title_fullStr Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL
title_full_unstemmed Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL
title_short Gender disparity in LDL-induced cardiovascular damage and the protective role of estrogens against electronegative LDL
title_sort gender disparity in ldl-induced cardiovascular damage and the protective role of estrogens against electronegative ldl
topic Original Investigation
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3974745/
https://www.ncbi.nlm.nih.gov/pubmed/24666525
http://dx.doi.org/10.1186/1475-2840-13-64
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