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Estradiol pretreatment attenuated nicotine-induced endothelial cell apoptosis via estradiol functional membrane receptor.

Abstract：

:Cigarette smoking is highly associated with increased cardiovascular disease complications. The female population, however, manifests reduced cardiovascular morbidity. We define nicotine's effect upon human umbilical vein endothelial cells (HUVECs), determine whether estradiol might ameliorate endothelial dysfunction via its membrane estrogen receptor (mER), and attempt to elucidate the underlying mechanisms. Endothelial cells were pretreated with estradiol-BSA and measured resultant ion flux across the cells via the patch clamp technique to assess mER is functionality. Estradiol-BSA administration was associated with 30% decreased nicotine-induced apoptosis and also attenuated nicotine-activated phosphorylation of p38 and ERK. Pretreatment of estradiol-BSA triggered a low calcium influx, suggesting ahead low influx calcium played a critical role in the underlying protective mechanisms of estradiol. Furthermore, this estradiol-BSA protection against apoptosis remained effective in the presence of tamoxifen, an intracellular estrogen receptor (iER) inhibitor. Additionally, tamoxifen did not abolish estradiol-BSA's inhibitory effect upon p38 and ERK's activation, giving evidence to the obligatory role of p38 and ERK signaling in the estradiol-BSA's anti-apoptotic action via mER. Our study provides evidence that nicotine enhances endothelial cell apoptosis, but estrogen exerts anti-apoptotic effect through its functional membrane estrogen receptor. Clinically, the nicotine in cigarettes might contribute to endothelial dysfunction, whereas ambient estradiol may provide cellular protection against nicotine-induced injury through its functional membrane receptor via MAPK pathway downregulation.

journal_name

Int Immunopharmacol

journal_title

International immunopharmacology

authors

Wang LL,Zhao JL,Lau WB,Zhang YQ,Qiao ZD,Wang YJ

doi

10.1016/j.intimp.2011.01.010

subject

Has Abstract

pub_date

2011-06-01 00:00:00

pages

675-82

issue

6

eissn

1567-5769

issn

1878-1705

pii

S1567-5769(11)00030-0

journal_volume

11

pub_type

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