PMID- 29660344
OWN - NLM
STAT- MEDLINE
DCOM- 20181126
LR  - 20211204
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Linking)
VI  - 503
IP  - 1
DP  - 2018 Sep 3
TI  - Hyperhomocysteinemia and hyperandrogenemia share PCSK9-LDLR pathway to disrupt 
      lipid homeostasis in PCOS.
PG  - 8-13
LID - S0006-291X(18)30847-7 [pii]
LID - 10.1016/j.bbrc.2018.04.078 [doi]
AB  - Women with polycystic ovary syndrome (PCOS) are at increased risk of 
      cardiovascular diseases (CVD); however, the independent role of PCOS in the 
      incident CVD remains unknown. There are reports that hyperhomocysteinemia (HHcy), 
      a potential cause of CVD, is frequently associated with PCOS. The present study 
      investigates the independent attributes of hyperandrogenemia (HA), the integral 
      associate of PCOS, and HHcy in causing atherogenic dyslipidemia. Twenty-five-day 
      old rats were treated with homocysteine (Hcy) at 50 mg/kg/day dose level for 12 
      weeks. The HepG2 cell lines transfected with siRNA directed to PCSK9 were 
      challenged with Hcy, homocysteine thiolactone (HTL), testosterone, 
      5alpha-dihydroxytestosterone (5alpha-DHT), or estradiol for 24 h. Rats administered with 
      Hcy developed HHcy and displayed PCOS-like phenotypes with adversely altered 
      lipid homeostasis and attenuated PI3K-AKT and Wnt signalling cascade. 
      Overexpression of steroidogenic acute regulatory protein (StAR) and 
      down-regulated expression of Aromatase together with elevated testosterone level 
      marked the state of HA. In culture, the HepG2 cells responded independently to 
      Hcy, HTL, testosterone, and 5alpha-DHT by an overt expression of PCSK9 and 
      down-regulated expression of LDLR. The effect was magnified under the combined 
      influence of Hcy and androgen(s). Estradiol, by contrast, exhibited the reverse 
      effect. The findings suggest that HA may independently attribute to an increased 
      cardiovascular risk in PCOS; however, the coexistence of HHcy catalyzes the risk 
      further.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Mondal, Kalyani
AU  - Mondal K
AD  - Reproductive Biology Research, CSIR-Indian Institute of Chemical Biology, 
      Jadavpur, Kolkata, 700032, WB, India.
FAU - Chakraborty, Pratip
AU  - Chakraborty P
AD  - Institute of Reproductive Medicine, Salt Lake City, Kolkata, 700106, WB, India.
FAU - Kabir, Syed N
AU  - Kabir SN
AD  - Reproductive Biology Research, CSIR-Indian Institute of Chemical Biology, 
      Jadavpur, Kolkata, 700032, WB, India. Electronic address: 
      snkabir@atgcdiagnostics.com.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20180618
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Androgens)
RN  - 0 (PCSK9 Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (Receptors, LDL)
RN  - EC 3.4.21.- (PCSK9 protein, human)
RN  - EC 3.4.21.- (Proprotein Convertase 9)
SB  - IM
MH  - Androgens/*blood
MH  - Animals
MH  - Cardiovascular Diseases/etiology/genetics/metabolism
MH  - Disease Models, Animal
MH  - Dyslipidemias/etiology/metabolism
MH  - Female
MH  - Gene Expression
MH  - Hep G2 Cells
MH  - Humans
MH  - Hyperhomocysteinemia/*complications/*metabolism
MH  - Lipid Metabolism
MH  - Metabolic Networks and Pathways
MH  - PCSK9 Inhibitors
MH  - Polycystic Ovary Syndrome/*complications/genetics/*metabolism
MH  - Proprotein Convertase 9/genetics/*metabolism
MH  - RNA, Small Interfering/genetics
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, LDL/genetics/*metabolism
MH  - Risk Factors
OTO - NOTNLM
OT  - Cardiovascular disease
OT  - Dyslipidemia
OT  - Hyperhomocysteinemia
OT  - Insulin resistance
OT  - Polycystic ovary syndrome
EDAT- 2018/04/17 06:00
MHDA- 2018/11/27 06:00
CRDT- 2018/04/17 06:00
PHST- 2018/04/03 00:00 [received]
PHST- 2018/04/10 00:00 [accepted]
PHST- 2018/04/17 06:00 [pubmed]
PHST- 2018/11/27 06:00 [medline]
PHST- 2018/04/17 06:00 [entrez]
AID - S0006-291X(18)30847-7 [pii]
AID - 10.1016/j.bbrc.2018.04.078 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2018 Sep 3;503(1):8-13. doi: 
      10.1016/j.bbrc.2018.04.078. Epub 2018 Jun 18.