Estrogen, neutrophils and oxidation.
The potential role of estrogens in the prevention of cardiovascular disease (CVD) is still under debate. Previous studies from our laboratory have shown that estradiol may act as a pro oxidant at physiological concentrations, enhancing peroxidase-mediated oxidation of low density lipoprotein (LDL). In the present study, we show that physiological concentrations of estradiol enhance fMLP-mediated neutrophil degranulation and oxidative stress markers. For example, 10 nM estradiol increased myeloperoxidase (MPO), elastase, and superoxide release by 19.9 +/- 9.6% (p = 0.006), 16.3 +/- 5.2% (p = 0.09), and 36.1 +/- 19.5% (p = 0.05), respectively. The enhancement of neutrophil degranulation by estradiol resulted in an increase in the formation of LDL oxidation markers such as conjugated dienes and thiobarbituric acid-reactive substances (20.7 +/- 7.2%, p = 0.04). Thus, estradiol can act as a pro oxidant, promoting neutrophil degranulation as well as reacting with MPO to enhance the oxidation of LDL. This mechanism supports our hypothesis that oxidative stress may be beneficial towards the prevention of CVD both by promoting plasma oxidation of LDL, with its subsequent clearance by the liver, as well as by inducing a threshold antioxidant defense in the arteries. Our study also suggests that estradiol by promoting oxidation in the plasma is beneficial in preventing CVD.
Chiang
Kenneth
K
Department of Pathology, LSU Health Science Center, 533 Bolivar St, # 747 CSRB, New Orleans, LA 70112, USA.
Parthasarathy
Sampath
S
Santanam
Nalini
N
D004967:Estrogens / Q000494:pharmacology*; D005966:Glucuronidase / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism*; D009113:Muramidase / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000201:enzymology; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects*; D010196:Pancreatic Elastase / Q000378:metabolism; D009195:Peroxidase / Q000378:metabolism; D010545:Peroxides / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D004967:Estrogens; D008077:Lipoproteins, LDL; D010545:Peroxides; D017392:Thiobarbituric Acid Reactive Substances; D013481:Superoxides; D009195:Peroxidase; D009113:Muramidase; D005966:Glucuronidase; D010196:Pancreatic Elastase