PMID- 27821559
OWN - NLM
STAT- MEDLINE
DCOM- 20170925
LR  - 20240324
IS  - 1933-7205 (Electronic)
IS  - 1933-7191 (Print)
IS  - 1933-7191 (Linking)
VI  - 23
IP  - 12
DP  - 2016 Dec
TI  - Sex Steroids Block the Initiation of Atherosclerosis.
PG  - 1620-1625
AB  - Atherosclerosis is the main cause of death in men and women. This so-called 
      "hardening of the arteries" results from advanced atherogenesis, the accumulation 
      and death of subendothelial fat-laden macrophages (vascular plaque). The 
      macrophages are attracted as the result of signals from injured vessels 
      recruiting and activating cells to quell the injury by inflammation. Among the 
      recruited cells are circulating monocytes that may be captured by the formation 
      of neural cell adhesion molecule (nCAM) tethers between the monocytes and 
      vascular endothelium; the tethers are dependent on electrostatic binding between 
      distal segments of apposed nCAM molecules. The capture of monocytes is followed 
      by their entry into the subendothelial area as macrophages, many of which will 
      remain and become the fat-laden foam cells in vascular plaque. Neural cell 
      adhesion molecules are subject to sialylation that blocks their electrostatic 
      binding. We showed that estradiol-induced nCAM sialylases are present in vascular 
      endothelial cells and tested whether sex steroid pretreatment of human vascular 
      endothelium could inhibit the capture of monocytes. Using in vitro techniques, 
      pretreatment of human arterial endothelial cells with estradiol, testosterone, 
      dehydroepiandrosterone and dihydrotestosterone all induced sialylation of 
      endothelial cells and, in a dose-response manner, reduced the capture of 
      monocytes. Steroid hormones are protective against atherogenesis and its 
      sequellae. Sex steroid depletion is associated with atherosclerosis. Based on 
      this knowledge plus our results using sex steroid pretreatment of endothelial 
      cells, we propose that the blockade of the initial step in atherogenesis by sex 
      steroid-induced nCAM sialylation may be crucial to hormonal prevention of 
      atherosclerosis.
CI  - (c) The Author(s) 2016.
FAU - Naftolin, Frederick
AU  - Naftolin F
AD  - Department of Obstetrics and Gynecology, New York University, New York, NY, USA 
      frederick.naftolin@nyumc.org.
FAU - Mehr, Holly
AU  - Mehr H
AD  - Department of Obstetrics and Gynecology, New York University, New York, NY, USA.
FAU - Fadiel, Ahmed
AU  - Fadiel A
AD  - Department of Obstetrics and Gynecology, New York University, New York, NY, USA.
LA  - eng
GR  - P01 HL076100/HL/NHLBI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Review
PL  - United States
TA  - Reprod Sci
JT  - Reproductive sciences (Thousand Oaks, Calif.)
JID - 101291249
RN  - 0 (Cell Adhesion Molecules)
RN  - 0 (Gonadal Steroid Hormones)
RN  - 08J2K08A3Y (Dihydrotestosterone)
RN  - 3XMK78S47O (Testosterone)
RN  - 459AG36T1B (Dehydroepiandrosterone)
RN  - 4TI98Z838E (Estradiol)
SB  - IM
MH  - Animals
MH  - Atherosclerosis/*metabolism/prevention & control
MH  - Cell Adhesion Molecules/*metabolism
MH  - Dehydroepiandrosterone/administration & dosage/metabolism
MH  - Dihydrotestosterone/administration & dosage/metabolism
MH  - Endothelium, Vascular/drug effects/*metabolism
MH  - Estradiol/administration & dosage/metabolism
MH  - Gonadal Steroid Hormones/administration & dosage/*metabolism
MH  - Humans
MH  - Monocytes/drug effects/*metabolism
MH  - Rats
MH  - Testosterone/administration & dosage/metabolism
PMC - PMC5933083
OTO - NOTNLM
OT  - atherogenesis
OT  - cardioprotection
OT  - estradiol
OT  - menopause
OT  - neural cell adhesion molecule
OT  - prevention
OT  - sex hormones
COIS- Declaration of Conflicting Interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2016/11/09 06:00
MHDA- 2017/09/26 06:00
PMCR- 2017/12/01
CRDT- 2016/11/09 06:00
PHST- 2016/11/09 06:00 [entrez]
PHST- 2016/11/09 06:00 [pubmed]
PHST- 2017/09/26 06:00 [medline]
PHST- 2017/12/01 00:00 [pmc-release]
AID - 23/12/1620 [pii]
AID - 10.1177_1933719116674078 [pii]
AID - 10.1177/1933719116674078 [doi]
PST - ppublish
SO  - Reprod Sci. 2016 Dec;23(12):1620-1625. doi: 10.1177/1933719116674078.