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

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.

• Authors: An-Sheng Lee, Wei-Yu Chen, Hua-Chen Chan, Jing-Fang Hsu, Ming-Yi Shen, Chia-Ming Chang, Henry Bair, Ming-Jai Su, Kuan-Cheng Chang, Chu-Huang Chen
• Journal: Cardiovascular diabetology (Cardiovasc Diabetol) Vol. 13 Pg. 64 (Mar 25 2014) ISSN: 1475-2840 [Electronic] England
• PMID: 24666525 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Estrogens
• Lipoproteins, LDL

Topics

• Animals
• Aorta (drug effects, pathology)
• Cardiovascular Diseases (pathology, prevention & control)
• Cattle
• Cells, Cultured
• DNA Damage (drug effects, physiology)
• Estrogens (pharmacology)
• Female
• Humans
• Lipoproteins, LDL (biosynthesis, toxicity)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Middle Aged
• Organ Culture Techniques
• Sex Characteristics