PMID- 33749307
OWN - NLM
STAT- MEDLINE
DCOM- 20211021
LR  - 20211021
IS  - 2047-9980 (Electronic)
IS  - 2047-9980 (Linking)
VI  - 10
IP  - 7
DP  - 2021 Apr 6
TI  - Deficiency of ITGAM Attenuates Experimental Abdominal Aortic Aneurysm in Mice.
PG  - e019900
LID - 10.1161/JAHA.120.019900 [doi]
LID - e019900
AB  - Background Integrin alphaM (CD11b), which is encoded by the Integrin Subunit Alpha M 
      (ITGAM) gene, is not only a surface marker of monocytes but also an essential 
      adhesion molecule. In this study, we investigated the effect of CD11b on 
      experimental abdominal aortic aneurysm and the potential underlying mechanisms. 
      Methods and Results The incidence of abdominal aortic aneurysm was not 
      significantly lower in ITGAM(-/-) mice than in control mice. Nevertheless, 
      knockout of CD11b reduced the maximum abdominal aortic diameter, macrophage 
      infiltration, matrix metalloproteinase-9 expression, and elastin and collagen 
      degradation. Additionally, lower expression of IL-6 was found in both the 
      peripheral blood and abdominal aortas of ITGAM(-/-) mice, indicating a biological 
      correlation between CD11b and the inflammatory response in abdominal aortic 
      aneurysm. In vitro, the number of ITGAM(-/-) bone marrow-derived macrophages 
      (BMDMs) that adhered to endothelial cells was significantly lower than the number 
      of wild-type BMDMs. Moreover, the CD11b monoclonal antibody and CD11b agonist 
      leukadherin-1 decreased and increased the number of adherent wild-type BMDMs, 
      respectively. Through RNA sequencing, genes associated with leukocyte 
      transendothelial migration were found to be downregulated in ITGAM(-/-) BMDMs. 
      Furthermore, immunoprecipitation-mass spectrometry analysis predicted that the 
      Akt pathway might be responsible for the impaired transmigratory ability of 
      ITGAM(-/-) BMDMs. The reduced activation of Akt was then confirmed, and the Akt 
      agonist SC79 partially rescued the transendothelial migratory function of 
      ITGAM(-/-) BMDMs. Conclusions CD11b might promote the development and progression 
      of abdominal aortic aneurysm by mediating the endothelial cells adhesion and 
      transendothelial migration of circulating monocytes/macrophages.
FAU - Zhou, Min
AU  - Zhou M
AD  - Department of Vascular Surgery Zhongshan Hospital Fudan University Shanghai 
      China.
FAU - Wang, Xia
AU  - Wang X
AD  - Department of Ultrasound in Medicine Shanghai Jiao Tong University Affiliated 
      Sixth People's Hospital Shanghai China.
FAU - Shi, Yiqin
AU  - Shi Y
AD  - Department of Nephrology Zhongshan Hospital Fudan University Shanghai China.
FAU - Ding, Yong
AU  - Ding Y
AD  - Department of Vascular Surgery Zhongshan Hospital Fudan University Shanghai 
      China.
FAU - Li, Xu
AU  - Li X
AD  - Department of Vascular Surgery Zhongshan Hospital Fudan University Shanghai 
      China.
FAU - Xie, Tianchen
AU  - Xie T
AD  - Department of Vascular Surgery Zhongshan Hospital Fudan University Shanghai 
      China.
FAU - Shi, Zhenyu
AU  - Shi Z
AD  - Department of Vascular Surgery Zhongshan Hospital Fudan University Shanghai 
      China.
FAU - Fu, Weiguo
AU  - Fu W
AD  - Department of Vascular Surgery Zhongshan Hospital Fudan University Shanghai 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210320
PL  - England
TA  - J Am Heart Assoc
JT  - Journal of the American Heart Association
JID - 101580524
RN  - 0 (CD11b Antigen)
RN  - 0 (Itgam protein, mouse)
RN  - 63231-63-0 (RNA)
SB  - IM
MH  - Animals
MH  - Aorta, Abdominal/*metabolism/pathology
MH  - Aortic Aneurysm, Abdominal/*genetics/metabolism/pathology
MH  - CD11b Antigen/biosynthesis/*genetics
MH  - Cells, Cultured
MH  - Disease Models, Animal
MH  - Disease Progression
MH  - Female
MH  - *Gene Expression Regulation
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - RNA/*genetics
PMC - PMC8174368
OTO - NOTNLM
OT  - abdominal aortic aneurysm
OT  - adhesion molecule
OT  - inflammation
OT  - integrin alphaM
OT  - migration
COIS- None.
EDAT- 2021/03/23 06:00
MHDA- 2023/02/25 06:00
PMCR- 2021/04/06
CRDT- 2021/03/22 12:22
PHST- 2021/03/23 06:00 [pubmed]
PHST- 2023/02/25 06:00 [medline]
PHST- 2021/03/22 12:22 [entrez]
PHST- 2021/04/06 00:00 [pmc-release]
AID - JAH36052 [pii]
AID - 10.1161/JAHA.120.019900 [doi]
PST - ppublish
SO  - J Am Heart Assoc. 2021 Apr 6;10(7):e019900. doi: 10.1161/JAHA.120.019900. Epub 
      2021 Mar 20.