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[Association between murine double minute 2 expression and AngII and ceramide induced endothelial cells apoptosis]
Li-xia Yang1, Dong Yang, Rui-wei Guo
1Department of Cardiology, Kunming General Hospital of Chengdu Army, Kunming 650032, China.
Objective:
To observe the relationship between murine double minute 2 (mdm2) expression and AngII and ceramide induced human umbilical endothelial cells apoptosis.
Method:
Human umbilical endothelial cells (ECs) were cultured in vitro and treated with angiotensin II alone or in combination with losartan (an inhibitor of AT1), PD123319 (an inhibitor of AT2) and FB1 (an inhibitor of ceramidase) respectively. ECs were also treated with different doses of C2-ceramide. The apoptosis of ECs was detected with Tunel, the mdm2 mRNA and protein expressions were measured with reverse transcription-polymerase chain reaction (RT-PCR) and Western blot.
Results:
PD123319 and FB1 but not losartan inhibited AngII induced ECs apoptosis and down-regulated the AngII induced increased mdm2 expressions. C2-ceramide also induces ECs apoptosis and down-regulated mdm2 expressions at protein and mRNA levels in a dose-dependent manner.
Conclusions:
AngII binding with AT2 induces ECs apoptosis via ceramide. AngII and ceramide induce EC apoptosis by inhibiting mdm2.
Insights
Angiotensin II (AngII) and ceramide trigger human umbilical endothelial cell apoptosis by inhibiting murine double minute 2 (mdm2) expression, particularly through the AT2 receptor pathway.
Area of Science:
- Endothelial cell biology
- Molecular mechanisms of apoptosis
- Cardiovascular research
Background:
- Endothelial cells play a crucial role in vascular health.
- Apoptosis of endothelial cells contributes to various vascular pathologies.
- The role of murine double minute 2 (mdm2) in AngII and ceramide-induced apoptosis requires further elucidation.
Purpose of the Study:
- To investigate the relationship between mdm2 expression and apoptosis in human umbilical endothelial cells (ECs) induced by Angiotensin II (AngII) and ceramide.
- To determine the specific receptor pathways involved in AngII-induced EC apoptosis.
Main Methods:
- Human umbilical ECs were cultured and treated with AngII, losartan (AT1 inhibitor), PD123319 (AT2 inhibitor), FB1 (ceramidase inhibitor), and C2-ceramide.
- Apoptosis was assessed using the Tunel assay.
- mdm2 mRNA and protein levels were quantified via RT-PCR and Western blot, respectively.
Main Results:
- AngII-induced EC apoptosis and increased mdm2 expression were inhibited by PD123319 and FB1, but not losartan.
- C2-ceramide induced EC apoptosis and down-regulated mdm2 expression in a dose-dependent manner at both mRNA and protein levels.
Conclusions:
- AngII binding to the AT2 receptor induces EC apoptosis through a ceramide-dependent mechanism.
- Both AngII and ceramide promote EC apoptosis by inhibiting mdm2 expression.
