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:C0149871 (
deep vein thrombosis
)
12,364
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Venous thromboembolism (VTE) constitutes a common cause of hospital-related morbidity and mortality, with the proverbial clinical feature of
deep venous thrombosis
(
DVT
). Endothelial cell injury and dysfunction comprise the critical contributor for the development of
DVT
. Lipoxin A4 (LXA4) fulfills pleiotropic roles in injury repair. However, its role in
DVT
remains poorly elucidated. In the present study, LXA4 supplementation dampened H
2
O
2
-evoked cytotoxic injury in human umbilical vein endothelial cells (HUVECs) by increasing cell viability, suppressing cell apoptosis and caspase-3 activity. Moreover, treatment with LXA4 afforded cytoprotective effects against oxidative stress damage in response to H
2
O
2
by abrogating ROS, lactate dehydrogenase (LDH) and MDA leakage, and elevating anti-oxidant SOD levels. Notably, LXA4 administration attenuated pro-vasoconstriction factor endothelin-1(ET-1) expression in HUVECs exposed to H
2
O
2
, but enhanced the productions of vasodilatation factor NO and prostacyclin (PGI2). Simultaneously, H
2
O
2
-induced high expression of pro-thrombotic Von Willebrand Factor (vWF) was also inhibited by LXA4. Mechanism analysis substantiated that LXA4 further augmented activation of the
Nrf2
-HO-1 pathway. Nevertheless, blocking this signaling via si-
Nrf2
transfection or HO-1 antagonist ZnPP both reversed LXA4-mediated effects against oxidative stress injury and thrombotic potential. Cessation of the LXA4 receptor pathway by its inhibitor Boc2 not only counteracted LXA4-evoked activation of the
Nrf2
-HO-1, but also reversed LXA4-mediated anti-oxidative stress and thrombosis-related factor expression. Accordingly, this study suggests that LXA4 may ameliorate vascular endothelial cell oxidative stress injury and subsequent thrombotic response via LXA4 receptor-dependent activation of the
Nrf2
-HO-1 signaling, implying a promising strategy for
DVT
and its complication.
...
PMID:Lipoxin A4 restores oxidative stress-induced vascular endothelial cell injury and thrombosis-related factor expression by its receptor-mediated activation of Nrf2-HO-1 axis. 3105 86
