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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...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2014
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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. |
format | Online Article Text |
id | pubmed-3974745 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
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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