PMID- 38036076
OWN - NLM
STAT- MEDLINE
DCOM- 20240202
LR  - 20240206
IS  - 1879-0038 (Electronic)
IS  - 0378-1119 (Linking)
VI  - 898
DP  - 2024 Mar 10
TI  - Hyperhomocysteinemia may aggravate abdominal aortic aneurysm formation by 
      up-regulating RASSF2.
PG  - 148036
LID - S0378-1119(23)00877-6 [pii]
LID - 10.1016/j.gene.2023.148036 [doi]
AB  - Abdominal aortic aneurysm (AAA) is a fatal cardiovascular disorder with high 
      mortality and morbidity rates. To date, no drug has shown to significantly 
      alleviate the risk of AAA. Previous studies have indicated that 
      hyperhomocysteinemia (HHcy) significantly increases the incidence of AAA by 
      disrupting endothelial cell homeostasis; however, the potential molecular 
      mechanisms require clarification. Herein, we aimed to integrate transcriptomics 
      analysis and molecular biology experiments to explore the potential molecular 
      targets by which HHcy may increase the incidence of AAA. We integrated two AAA 
      data profiles (GSE57691 and GSE7084) based on previously published microarray 
      ribonucleic acid sequencing (RNAseq) data from the GEO database. Additionally, 
      500 muM homocysteine-treated human aorta endothelium cells microarray dataset 
      (GSE175748) was downloaded and processed. Subsequently, single-cell RNA-seq 
      profiles of the aortic aneurysms (GSE155468) were downloaded, scaled, and 
      processed for further analysis. The microarray profiles analysis demonstrated 
      that the Ras association domain family member 2 (RASSF2) and interleukin (IL)-1beta 
      are potentially the target genes involved in the HHcy-mediated aggravation of AAA 
      formation. Single-cell RNAseq analysis revealed that RASSF2 might impair 
      endothelial cell function by increasing inflammatory cell infiltration to 
      participate in AAA formation. Finally, we conducted reverse transcription 
      quantitative polymerase chain reaction and immunofluorescence analysis to 
      validate the up-regulated mRNA expression of RASSF2 (p = 0.008) and IL-1beta 
      (p = 0.002) in AAA tissue compared to control tissue. Immunofluorescence staining 
      revealed overexpression of RASSF2 protein in AAA tissue sections compared to 
      control tissue (p = 0.037). Co-localization of RASSF2 and the aortic endothelium 
      cell marker, CD31, was observed in tissue sections, indicating the potential 
      involvement of RASSF2 in aortic endothelial cells. To summarise, our preliminary 
      study revealed that HHcy may worsen AAA formation by up-regulating the expression 
      of RASSF2 and IL-1beta in aortic endothelium cells.
CI  - Copyright (c) 2023. Published by Elsevier B.V.
FAU - Liu, Zongwei
AU  - Liu Z
AD  - Department of Vascular surgery of Tianjin Medical University General Hospital, 
      Tianjin, PR China.
FAU - Feng, Guilin
AU  - Feng G
AD  - Department of Vascular surgery of Tianjin Medical University General Hospital, 
      Tianjin, PR China.
FAU - Chen, Yonghui
AU  - Chen Y
AD  - Department of Vascular surgery of Tianjin Medical University General Hospital, 
      Tianjin, PR China.
FAU - Fan, Jibo
AU  - Fan J
AD  - Department of Vascular surgery of Tianjin Medical University General Hospital, 
      Tianjin, PR China.
FAU - Liang, Zhian
AU  - Liang Z
AD  - Department of Vascular surgery of Tianjin Medical University General Hospital, 
      Tianjin, PR China.
FAU - Bi, Jiaxue
AU  - Bi J
AD  - Department of Vascular surgery of Tianjin Medical University General Hospital, 
      Tianjin, PR China. Electronic address: bijiaxue@126.com.
FAU - Dai, Xiangchen
AU  - Dai X
AD  - Department of Vascular surgery of Tianjin Medical University General Hospital, 
      Tianjin, PR China. Electronic address: 13302165917@163.com.
LA  - eng
PT  - Journal Article
DEP - 20231128
PL  - Netherlands
TA  - Gene
JT  - Gene
JID - 7706761
RN  - 0 (RASSF2 protein, human)
RN  - 0 (Tumor Suppressor Proteins)
SB  - IM
MH  - Humans
MH  - *Hyperhomocysteinemia/complications/genetics/metabolism
MH  - Endothelial Cells/metabolism
MH  - *Aortic Aneurysm, Abdominal/genetics/metabolism
MH  - Gene Expression Profiling
MH  - Endothelium, Vascular/metabolism
MH  - Tumor Suppressor Proteins/genetics
OTO - NOTNLM
OT  - Abdominal aortic aneurysm
OT  - Hyperhomocysteinemia
OT  - Ras association domain family member 2
OT  - Single cell RNAseq
COIS- Declaration of competing interest The authors declare that they have no known 
      competing financial interests or personal relationships that could have appeared 
      to influence the work reported in this paper.
EDAT- 2023/12/01 00:43
MHDA- 2024/02/02 06:42
CRDT- 2023/11/30 21:55
PHST- 2023/09/09 00:00 [received]
PHST- 2023/11/14 00:00 [revised]
PHST- 2023/11/24 00:00 [accepted]
PHST- 2024/02/02 06:42 [medline]
PHST- 2023/12/01 00:43 [pubmed]
PHST- 2023/11/30 21:55 [entrez]
AID - S0378-1119(23)00877-6 [pii]
AID - 10.1016/j.gene.2023.148036 [doi]
PST - ppublish
SO  - Gene. 2024 Mar 10;898:148036. doi: 10.1016/j.gene.2023.148036. Epub 2023 Nov 28.