Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0004153 (
atherosclerosis
)
77,401
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Eotaxin-2 is a potent chemoattractant. High concentration of eotaxin-2 triggers the inflammation and tumor metastasis. Inhibition of eotaxin-2 may protect experimental atherogenesis although the mechanism is still unclear. Toll-like receptor 4 (TLR4) plays a major role mediating vascular inflammation, which is related to atherogenesis. In the results, we demonstrated that eotaxin-2 potentially impairs the tube formation capacity of human coronary artery endothelial cells (HCAECs). Eotaxin-2 augments the monocytic adhesion in lipopolysaccharides (LPS)-induced HCAECs, and which were reversed by TLR4 siRNA. Thus this study was conducted to investigate whether eotaxin-2 increases TLR4 expression, and then enhances the sensitivity of cells to antigen stimulation in HCAECs, which mediates the increasing of the development of serious
atherosclerosis
. In fact, we showed that JNK/SAPK, p38 MAPK, and ERK1/2 activation contribute to the transcriptional signaling pathway, JNK/SAPK and p38 MAPK regulate post-transcriptional modification, as well as protein-trafficking pathway in eotaxin-2-treated HCAECs TLR4 expression. RNA binding proteins, such as human antigen R (HuR) and tristetraprolin (TTP) mediate stability of TLR4 mRNA and chaperone, such as
PRAT4A
(a protein associated with TLR4) regulate trafficking of TLR4 protein might confer eotaxin-2 responsiveness. Eotaxin-2 administration led to a significant elevation of high cholesterol diet-induced
atherosclerosis
, and of TLR4 expression in B6.129S7-
Ldlr
tm1Her
/J but not
Ldlr
-/--/-/
Tlr4
-/-
mice. Our results revealed that eotaxin-2 induced overexpression TLR4 via mitogen-activated protein kinases (MAPK) signaling pathways, RNA binding proteins-mediated mRNA stabilization, and
PRAT4A
-regulated trafficking in HCAECs. These effects may lead to amplification of inflammatory responses contribute to the pathogenesis of cardiovascular disorders.
...
PMID:Eotaxin-2 increased toll-like receptor 4 expression in endothelial cells
in vitro
and exacerbates high-cholesterol diet-induced atherogenesis
in vivo
. 2807 7
