PMID- 30683311
OWN - NLM
STAT- MEDLINE
DCOM- 20191129
LR  - 20200309
IS  - 1090-2104 (Electronic)
IS  - 0006-291X (Print)
IS  - 0006-291X (Linking)
VI  - 510
IP  - 1
DP  - 2019 Feb 26
TI  - Hyperhomocysteinemia induced endothelial progenitor cells dysfunction through 
      hyper-methylation of CBS promoter.
PG  - 135-141
LID - S0006-291X(19)30080-4 [pii]
LID - 10.1016/j.bbrc.2019.01.066 [doi]
AB  - Bone marrow (BM)-derived endothelial progenitor cells (EPCs) are the key players 
      in angiogenesis and vascular function. Cystathionine-beta-synthase (CBS), an 
      H(2)S-generating enzyme in methionine metabolism, regulates the function of these 
      EPCs. This study aims to examine whether CBS hyper-methylation contributes to the 
      bone marrow endothelial progenitor cell (BM-EPCs) function and subsequent bone 
      blood flow in mice fed with a high methionine diet (HMD). Bone marrow (BM) cells 
      were collected from HMD and control mice, differentiated into BM-EPCs, and were 
      characterized by acLDL-DiI labeling. CBS mRNA expression was analyzed by 
      real-time PCR, and the global methylation status and methylation of the CBS 
      promoter were detected by nuclear 5-mC assay and methylation-specific PCR (qMSP) 
      respectively. The result reveals that CBS promoter in BM-EPCs from HMD mice was 
      hyper-methylated and the methylation level was, indeed, negatively correlated 
      with CBS mRNA and angiogenic function of BM-EPCs. In addition, global methylation 
      (5-mC) and DNA methyltransferase-1 (DNMT1) expression were increased in HMD 
      condition. In vitro study also shows that HMD induced hyperhomocysteinemia (HHcy) 
      impaired both adhesion and angiogenesis properties of BM-EPCs, accompanied by 
      higher methylation level of CBS promoter that compared to control. Furthermore, 
      bone blood flow was found to be decreased in HMD mice as compared to wild-type 
      mice. To dissect the epigenetic mechanism, we also administrated DNMT inhibitor, 
      5-azacytidine (5-Aza) to HMD mice. The administration of 5-Aza in HMD mice 
      restored the CBS expression, EPC mediated angiogenesis and blood flow by reducing 
      abnormal DNA hyper-methylation. In conclusion, HHcy dismantles BM-EPCs function 
      and bone blood flow through the hyper-methylation of the CBS promoter in HMD fed 
      mice.
CI  - Copyright (c) 2019 Elsevier Inc. All rights reserved.
FAU - Behera, Jyotirmaya
AU  - Behera J
AD  - Bone Biology Laboratory, Department of Physiology, School of Medicine, University 
      of Louisville, Louisville, KY 40202, USA.
FAU - Tyagi, Suresh C
AU  - Tyagi SC
AD  - Bone Biology Laboratory, Department of Physiology, School of Medicine, University 
      of Louisville, Louisville, KY 40202, USA.
FAU - Tyagi, Neetu
AU  - Tyagi N
AD  - Bone Biology Laboratory, Department of Physiology, School of Medicine, University 
      of Louisville, Louisville, KY 40202, USA. Electronic address: 
      n0tyag01@louisville.edu.
LA  - eng
GR  - R01 AR067667/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20190123
PL  - United States
TA  - Biochem Biophys Res Commun
JT  - Biochemical and biophysical research communications
JID - 0372516
RN  - 0 (Angiogenesis Inducing Agents)
RN  - AE28F7PNPL (Methionine)
RN  - EC 2.1.1.- (Methyltransferases)
RN  - EC 4.2.1.22 (Cystathionine beta-Synthase)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Angiogenesis Inducing Agents
MH  - Animals
MH  - Azacitidine/pharmacology
MH  - Bone Marrow Cells
MH  - Bone and Bones/blood supply
MH  - Cell Differentiation
MH  - Cystathionine beta-Synthase/*genetics
MH  - *DNA Methylation
MH  - Endothelial Progenitor Cells/*pathology
MH  - Hyperhomocysteinemia/*pathology
MH  - Methionine/metabolism
MH  - Methyltransferases/antagonists & inhibitors
MH  - Mice
MH  - *Promoter Regions, Genetic
MH  - Regional Blood Flow
PMC - PMC6666267
MID - NIHMS1038890
OTO - NOTNLM
OT  - Angiogenesis
OT  - BM-EPCs
OT  - Blood flow
OT  - CpG islands
OT  - DNA hyper-methylation
OT  - DNMTs
COIS- Disclosure of interest The authors declare that there is no conflict of interest.
EDAT- 2019/01/27 06:00
MHDA- 2019/11/30 06:00
PMCR- 2019/07/30
CRDT- 2019/01/27 06:00
PHST- 2019/01/09 00:00 [received]
PHST- 2019/01/12 00:00 [accepted]
PHST- 2019/01/27 06:00 [pubmed]
PHST- 2019/11/30 06:00 [medline]
PHST- 2019/01/27 06:00 [entrez]
PHST- 2019/07/30 00:00 [pmc-release]
AID - S0006-291X(19)30080-4 [pii]
AID - 10.1016/j.bbrc.2019.01.066 [doi]
PST - ppublish
SO  - Biochem Biophys Res Commun. 2019 Feb 26;510(1):135-141. doi: 
      10.1016/j.bbrc.2019.01.066. Epub 2019 Jan 23.