RGD Reference Report - 2K1C-activated Angiotensin II (Ang II) exacerbates vascular damage in a rat model of arthritis through the ATR/ERK1/2 signaling pathway. - Rat Genome Database

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2K1C-activated Angiotensin II (Ang II) exacerbates vascular damage in a rat model of arthritis through the ATR/ERK1/2 signaling pathway.

Authors: Zhang, Ying  Luo, Xuexia  Zhou, Yue  Wu, Huaxun  Chen, Jingyu  Wang, Ying  Chen, Danian  Xu, Zhouwei  Yan, Shangxue  Wei, Wei 
Citation: Zhang Y, etal., Inflamm Res. 2017 Oct;66(10):881-890. doi: 10.1007/s00011-017-1069-8. Epub 2017 Jun 26.
RGD ID: 13513975
Pubmed: PMID:28653218   (View Abstract at PubMed)
DOI: DOI:10.1007/s00011-017-1069-8   (Journal Full-text)


OBJECTIVE: To explore the role and mechanism of the two-kidney one-clip (2K1C)-activated Angiotensin II (Ang II) in the development of vascular damage in adjuvant-induced arthritis (AA) rats.
METHODS: 2K1C rats were established in normal and AA rats for 35 days. Hypertension, endothelial dysfunction, and vascular hypertrophy induced by 2K1C-activated Ang II in systemic inflammation rats were evaluated. The levels of Ang II and TNF-α in serum were observed by ELISA kits. Expressions of Ang II/ATR/ERK1/2 signaling pathway molecules in the aorta were tested by immunohistochemistry or western blot. The migration and capillary tube formation abilities of human umbilical vein endothelial cells (HUVECs) were tested by migration chamber and capillary tube formation assays.
RESULTS: The level of Ang II in serum was significantly increased in 2K1C rats. Compared with AA rats, the high level of Ang II activated by 2K1C reduced the endothelium-dependent vasodilator responses to acetylcholine (ACh) in the thoracic aorta and exacerbated endothelial dysfunction and vascular hypertrophy. Expressions of ATR, GRK2, p-ERK1/2, and p-NF-κB were significantly increased in the aorta of AA combined with 2K1C rats. The migration and capillary tube formation abilities of HUVECs were significantly enhanced by Ang II and TNF-α co-stimulations in vitro through the ATR/ERK1/2 signaling pathway compared to those stimulated with TNF-α.
CONCLUSIONS: 2K1C-activated Ang II is involved in aggravated vascular injury and endothelial dysfunction through the ATR/ERK1/2 signaling pathway in AA rats.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GRK2HumanExperimental Arthritis  ISOGrk2 (Rattus norvegicus)protein:increased expression:aorta (rat)RGD 
Grk2RatExperimental Arthritis  IEP protein:increased expression:aorta (rat)RGD 
Grk2MouseExperimental Arthritis  ISOGrk2 (Rattus norvegicus)protein:increased expression:aorta (rat)RGD 
GRK2HumanVascular System Injuries  ISOGrk2 (Rattus norvegicus)protein:increased expression:aorta (rat)RGD 
Grk2RatVascular System Injuries  IEP protein:increased expression:aorta (rat)RGD 
Grk2MouseVascular System Injuries  ISOGrk2 (Rattus norvegicus)protein:increased expression:aorta (rat)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Grk2  (G protein-coupled receptor kinase 2)

Genes (Mus musculus)
Grk2  (G protein-coupled receptor kinase 2)

Genes (Homo sapiens)
GRK2  (G protein-coupled receptor kinase 2)


Additional Information