PMID- 34147541
OWN - NLM
STAT- MEDLINE
DCOM- 20220110
LR  - 20220110
IS  - 1872-7972 (Electronic)
IS  - 0304-3940 (Linking)
VI  - 760
DP  - 2021 Aug 24
TI  - Simvastatin increases circulating endothelial progenitor cells and inhibits the 
      formation of intracranial aneurysms in rats with diet-induced 
      hyperhomocysteinemia.
PG  - 136072
LID - S0304-3940(21)00450-X [pii]
LID - 10.1016/j.neulet.2021.136072 [doi]
AB  - BACKGROUND AND PURPOSE: Endothelial dysfunction triggers early pathological 
      changes in artery, leading to the formation of intracranial aneurysm (ICA). 
      Increase in plasma homocysteine (Hcy) impairs endothelium and endothelial 
      progenitor cells (EPCs) are critical in repairing damaged endothelium. The aim of 
      this study was to assess the impact of simvastatin on ICA formation in rats with 
      hyperhomocysteinemia (HHcy). METHODS: ICAs were induced in Male Sprague-Dawley 
      rats after surgical induction in the presence of HHcy induced by a high 
      L-methionine diet with or without oral simvastatin treatment. The size and media 
      thickness of ICAs were evaluated 2 months after aneurysm induction. EPCs and 
      serum vascular endothelial grow factor (VEGF) were measured be flow cytometry and 
      ELISA respectively. Plasma Hcy levels and expression of VEGF, endothelial nitric 
      oxide synthase (eNOS), inducible nitric oxide synthase (iNOS), matrix 
      metalloproteinase-2 (MMP-2), and MMP-9 in aneurysmal walls were examined and 
      correlated with ICA formation. RESULTS: HHcy accelerates ICA formation and rats 
      treated with simvastatin exhibited a significant increase in media thickness and 
      a reduction in aneurysmal size. Simvastatin increased levels of circulating EPCs 
      and decreased iNOS, MMP-2, MMP-9 and VEGF mRNA levels, while increased eNOS mRNA 
      in aneurysmal tissue. CONCLUSION: In a rat model, HHcy reduces circulating EPCs 
      and accelerates ICA formation. Simvastatin treatment increases circulating EPCs 
      and inhabits the formation of ICA. We have shown a close association among 
      circulating EPCs, biochemical markers related to vascular remodeling and the 
      formation of ICA.
CI  - Copyright (c) 2021 Elsevier B.V. All rights reserved.
FAU - Xu, Yong
AU  - Xu Y
AD  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing, China; Department of Neurosurgery, Beijing Tongren Hospital, Capital 
      Medical University, Beijing, China.
FAU - Zhang, Bin
AU  - Zhang B
AD  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing, China.
FAU - Chen, Yu
AU  - Chen Y
AD  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing, China.
FAU - Wang, Xiu
AU  - Wang X
AD  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing, China.
FAU - Li, Yong
AU  - Li Y
AD  - Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, 
      Beijing, China.
FAU - Wu, Jiangping
AU  - Wu J
AD  - Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, 
      Beijing, China.
FAU - Dong, Hao
AU  - Dong H
AD  - Department of Neurosurgery, Beijing Tongren Hospital, Capital Medical University, 
      Beijing, China.
FAU - Wang, Shuo
AU  - Wang S
AD  - Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, 
      Beijing, China. Electronic address: captain9858@126.com.
LA  - eng
PT  - Journal Article
DEP - 20210617
PL  - Ireland
TA  - Neurosci Lett
JT  - Neuroscience letters
JID - 7600130
RN  - 0 (Biomarkers)
RN  - 0 (Hydroxymethylglutaryl-CoA Reductase Inhibitors)
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - AGG2FN16EV (Simvastatin)
SB  - IM
MH  - Animals
MH  - Biomarkers/blood
MH  - Disease Models, Animal
MH  - Endothelial Progenitor Cells/*drug effects
MH  - Endothelium, Vascular/drug effects/pathology
MH  - Homocysteine/blood
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacology/therapeutic use
MH  - Hyperhomocysteinemia/blood/complications/*drug therapy
MH  - Intracranial Aneurysm/blood/etiology/pathology/*prevention & control
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Simvastatin/*pharmacology/therapeutic use
MH  - Vascular Remodeling/drug effects
OTO - NOTNLM
OT  - Endothelial progenitor cells
OT  - Homocysteine
OT  - Hyperhomocysteinemia
OT  - Intracranial cerebral aneurysm
OT  - Simvastatin
EDAT- 2021/06/21 06:00
MHDA- 2022/01/11 06:00
CRDT- 2021/06/20 20:35
PHST- 2021/04/08 00:00 [received]
PHST- 2021/06/01 00:00 [revised]
PHST- 2021/06/15 00:00 [accepted]
PHST- 2021/06/21 06:00 [pubmed]
PHST- 2022/01/11 06:00 [medline]
PHST- 2021/06/20 20:35 [entrez]
AID - S0304-3940(21)00450-X [pii]
AID - 10.1016/j.neulet.2021.136072 [doi]
PST - ppublish
SO  - Neurosci Lett. 2021 Aug 24;760:136072. doi: 10.1016/j.neulet.2021.136072. Epub 
      2021 Jun 17.