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

Lee AS, Chen WY, Chan HC, Hsu JF, Shen MY, Chang CM, Bair H, Su MJ, Chang KC, Chen CH - Cardiovasc Diabetol (2014)

Bottom Line: L5 levels were compared between middle-aged men and age-matched, premenopausal women with or without MetS.We also studied the protective effects of 17β-estradiol and genistein against electronegative LDL-induced senescence in cultured bovine aortic endothelial cells (BAECs).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiology, China Medical University Hospital, Taichung City, Taiwan. kuancheng.chang@gmail.com.

ABSTRACT

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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Related in: MedlinePlus

Effect of LDL electronegativity and estrogens on bovine aortic endothelial cell (BAEC) senescence. A, Representative images of SA-β-gal staining of senescent BAECs (blue) 5 days after incubation with 30 μg/mL LDL isolated from male or female db/db or wild-type mice in the presence or absence of pretreatment with 17β-estradiol (10 nM) or genistein (100 nM). B, The percentage of senescent cells and (C) telomerase activity in BAECs treated with LDL from male or female db/db or wild-type mice in the presence or absence of 17β-estradiol or genistein. n = 4 for each group. *P < 0.01 vs. gender-matched wild-type LDL, #P < 0.05 and ##P < 0.01 vs. gender-matched db/db LDL.
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Figure 4: Effect of LDL electronegativity and estrogens on bovine aortic endothelial cell (BAEC) senescence. A, Representative images of SA-β-gal staining of senescent BAECs (blue) 5 days after incubation with 30 μg/mL LDL isolated from male or female db/db or wild-type mice in the presence or absence of pretreatment with 17β-estradiol (10 nM) or genistein (100 nM). B, The percentage of senescent cells and (C) telomerase activity in BAECs treated with LDL from male or female db/db or wild-type mice in the presence or absence of 17β-estradiol or genistein. n = 4 for each group. *P < 0.01 vs. gender-matched wild-type LDL, #P < 0.05 and ##P < 0.01 vs. gender-matched db/db LDL.

Mentions: To test our hypothesis that LDL with increased electronegativity induces vascular senescence, we exposed BAECs to LDL from male or female db/db or wild-type mice and analyzed SA-β-gal staining and telomerase activity in the treated cells. BAECs treated with LDL from male db/db mice had a significantly higher percentage of SA-β-gal–positive stained cells (P < 0.01) and a significantly lower amount of telomerase activity (P < 0.01) than did BAECs treated with LDL from male wild-type mice (Figure 4). In addition, BAECs treated with LDL from female db/db mice had a significantly higher percentage of SA-β-gal–positive stained cells (P < 0.01) and a significantly lower amount of telomerase activity (P < 0.01) than did BAECs treated with LDL from female wild-type mice, although the effects of LDL from female db/db mice were not as strong as those of LDL from male db/db mice (Figure 4). Furthermore, when we examined whether estrogens confer protection against LDL from db/db mice, we found that pretreatment of BAECs with 17β-estradiol (10 nM) or genistein (100 nM) significantly attenuated the percentage of SA-β-gal–stained cells and blocked the effects on telomerase activity induced by LDL from male or female db/db mice (P < 0.01 or P < 0.05) (Figure 4).


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

Lee AS, Chen WY, Chan HC, Hsu JF, Shen MY, Chang CM, Bair H, Su MJ, Chang KC, Chen CH - Cardiovasc Diabetol (2014)

Effect of LDL electronegativity and estrogens on bovine aortic endothelial cell (BAEC) senescence. A, Representative images of SA-β-gal staining of senescent BAECs (blue) 5 days after incubation with 30 μg/mL LDL isolated from male or female db/db or wild-type mice in the presence or absence of pretreatment with 17β-estradiol (10 nM) or genistein (100 nM). B, The percentage of senescent cells and (C) telomerase activity in BAECs treated with LDL from male or female db/db or wild-type mice in the presence or absence of 17β-estradiol or genistein. n = 4 for each group. *P < 0.01 vs. gender-matched wild-type LDL, #P < 0.05 and ##P < 0.01 vs. gender-matched db/db LDL.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
Show All Figures
getmorefigures.php?uid=PMC3974745&req=5

Figure 4: Effect of LDL electronegativity and estrogens on bovine aortic endothelial cell (BAEC) senescence. A, Representative images of SA-β-gal staining of senescent BAECs (blue) 5 days after incubation with 30 μg/mL LDL isolated from male or female db/db or wild-type mice in the presence or absence of pretreatment with 17β-estradiol (10 nM) or genistein (100 nM). B, The percentage of senescent cells and (C) telomerase activity in BAECs treated with LDL from male or female db/db or wild-type mice in the presence or absence of 17β-estradiol or genistein. n = 4 for each group. *P < 0.01 vs. gender-matched wild-type LDL, #P < 0.05 and ##P < 0.01 vs. gender-matched db/db LDL.
Mentions: To test our hypothesis that LDL with increased electronegativity induces vascular senescence, we exposed BAECs to LDL from male or female db/db or wild-type mice and analyzed SA-β-gal staining and telomerase activity in the treated cells. BAECs treated with LDL from male db/db mice had a significantly higher percentage of SA-β-gal–positive stained cells (P < 0.01) and a significantly lower amount of telomerase activity (P < 0.01) than did BAECs treated with LDL from male wild-type mice (Figure 4). In addition, BAECs treated with LDL from female db/db mice had a significantly higher percentage of SA-β-gal–positive stained cells (P < 0.01) and a significantly lower amount of telomerase activity (P < 0.01) than did BAECs treated with LDL from female wild-type mice, although the effects of LDL from female db/db mice were not as strong as those of LDL from male db/db mice (Figure 4). Furthermore, when we examined whether estrogens confer protection against LDL from db/db mice, we found that pretreatment of BAECs with 17β-estradiol (10 nM) or genistein (100 nM) significantly attenuated the percentage of SA-β-gal–stained cells and blocked the effects on telomerase activity induced by LDL from male or female db/db mice (P < 0.01 or P < 0.05) (Figure 4).

Bottom Line: L5 levels were compared between middle-aged men and age-matched, premenopausal women with or without MetS.We also studied the protective effects of 17β-estradiol and genistein against electronegative LDL-induced senescence in cultured bovine aortic endothelial cells (BAECs).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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Division of Cardiology, China Medical University Hospital, Taichung City, Taiwan. kuancheng.chang@gmail.com.

ABSTRACT

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.

Show MeSH
Related in: MedlinePlus