PMID- 38430022
OWN - NLM
STAT- MEDLINE
DCOM- 20240304
LR  - 20240314
IS  - 1165-158X (Electronic)
IS  - 0145-5680 (Linking)
VI  - 70
IP  - 2
DP  - 2024 Feb 29
TI  - Homocysteine modulates CXCL10/CXCR3 axis activity to induce endothelial 
      dysfunction.
PG  - 197-204
LID - 10.14715/cmb/2024.70.2.28 [doi]
AB  - Elevated homocysteine (Hcy) levels have been linked to the development of 
      cardiovascular diseases, notably endothelial dysfunction, a critical precursor to 
      atherosclerosis. In this extensive investigation, we explore the intricate 
      pathways through which Hcy influences endothelial dysfunction, with particular 
      attention to the CXCL10/CXCR3 axis. Employing a dual approach encompassing both 
      in vitro and in vivo models, we scrutinize the repercussions of Hcy exposure on 
      endothelial functionality. Our results reveal that Hcy significantly impairs 
      crucial endothelial processes, including cell migration, proliferation, and tube 
      formation. Concomitantly, Hcy upregulates the expression of adhesion molecules, 
      exacerbating endothelial dysfunction. In a murine hyperhomocysteinemia (HHcy) 
      model, we observed a parallel increase in plasma Hcy levels and adverse vascular 
      effects. Moreover, our study unraveled a pivotal role of the CXCL10/CXCR3 axis in 
      Hcy-induced endothelial dysfunction. Hcy exposure led to the upregulation of 
      CXCL10 and CXCR3, both in vitro and in HHcy mice. Importantly, the blockade of 
      this axis, achieved through specific antibodies or NBI-74330, mitigated the 
      detrimental effects of Hcy on endothelial function. In conclusion, our findings 
      illuminated the central role of the CXCL10/CXCR3 axis in mediating Hcy-induced 
      endothelial dysfunction, providing valuable insights for potential therapeutic 
      strategies in managing HHcy-related cardiovascular diseases.
FAU - Xu, Yanjie
AU  - Xu Y
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China. xuyanjie13@163.com.
FAU - Xu, Yingying
AU  - Xu Y
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China. echoxuying@163.com.
FAU - Yu, Zuozong
AU  - Yu Z
AD  - Department of Cardiovascular Medicine, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China. Yuzz9494@qq.com.
FAU - He, Dingwen
AU  - He D
AD  - Department of Orthopaedics, The Second Affiliated Hospital of Nanchang 
      University, Nanchang, Jiangxi 330006, China. hedingwen@126.com.
LA  - eng
PT  - Journal Article
DEP - 20240229
PL  - France
TA  - Cell Mol Biol (Noisy-le-grand)
JT  - Cellular and molecular biology (Noisy-le-Grand, France)
JID - 9216789
RN  - 0LVT1QZ0BA (Homocysteine)
RN  - 0 (Chemokine CXCL10)
RN  - 0 (Receptors, CXCR3)
SB  - IM
MH  - Animals
MH  - Mice
MH  - *Cardiovascular Diseases
MH  - Homocysteine/pharmacology
MH  - Up-Regulation
MH  - *Chemokine CXCL10/metabolism
MH  - *Receptors, CXCR3/metabolism
EDAT- 2024/03/02 12:44
MHDA- 2024/03/04 06:49
CRDT- 2024/03/02 04:32
PHST- 2023/12/12 00:00 [received]
PHST- 2024/03/04 06:49 [medline]
PHST- 2024/03/02 12:44 [pubmed]
PHST- 2024/03/02 04:32 [entrez]
AID - 10.14715/cmb/2024.70.2.28 [doi]
PST - epublish
SO  - Cell Mol Biol (Noisy-le-grand). 2024 Feb 29;70(2):197-204. doi: 
      10.14715/cmb/2024.70.2.28.