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Published on: January 19, 2019
Serum UCH-L1 as a Novel Biomarker to Predict Neuronal Apoptosis Following Deep Hypothermic Circulatory Arrest
Ya-Ping Zhang1, Yao-Bin Zhu1, Dayue Darrel Duan2
11. Pediatric Heart Center, Beijing Anzhen Hospital, Capital Medical University, Beijing, China 100029.
Insights
Deep hypothermic circulatory arrest (DHCA) can cause brain cell death. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) levels can predict this neuronal apoptosis, acting as a potential biomarker for DHCA.
Area of Science:
- Neuroscience
- Cardiovascular Surgery
- Biomarker Discovery
Background:
- Deep hypothermic circulatory arrest (DHCA) is utilized in complex infant cardiac surgeries and aortic dissection repair.
- DHCA poses a risk of inducing neuronal apoptotic cell death in the brain.
- Elevated serum ubiquitin C-terminal hydrolase L1 (UCH-L1) is associated with neurological diseases involving neuronal injury.
Purpose of the Study:
- To investigate the hypothesis that UCH-L1 may serve as a potential biomarker for DHCA-induced ischemic neuronal apoptosis.
- To evaluate the correlation between serum UCH-L1 levels and the extent of neuronal apoptosis following DHCA.
Main Methods:
- Anesthetized piglets underwent cardiopulmonary bypass (CPB) with a 1-hour DHCA period followed by rewarming.
- Serum UCH-L1 levels were measured, and neuronal apoptosis, along with Bax and Bcl-2 protein expression in the hippocampus, were assessed.
- Receiver operating characteristic (ROC) curves and correlation analysis were employed to determine the relationship between neuronal apoptosis and UCH-L1 levels.
Main Results:
- DHCA led to significant neuronal apoptosis, increased Bax:Bcl-2 ratio in the hippocampus, and elevated serum UCH-L1 levels (P<0.05).
- A positive correlation was observed between serum UCH-L1 levels and the severity of neuronal apoptosis (r=0.78, P<0.01).
- ROC analysis indicated UCH-L1 as a predictor of neuronal apoptosis with 85% sensitivity and 57% specificity at a cutoff of 0.25.
Conclusions:
- Serum UCH-L1 is a readily measurable biomarker capable of predicting DHCA-induced neural apoptosis.
- Increased UCH-L1 concentration correlates with the severity of neural apoptosis following DHCA.
Background:
Deep hypothermic circulatory arrest (DHCA) has been used in cardiac surgery involving infant complex congenital heart disease and aortic dissection. DHCA carries a risk of neuronal apoptotic death in brain. Serum ubiquitin C-terminal hydrolase L1 (UCH-L1) level is elevated in a number of neurological diseases involving neuron injury and death. We studied the hypothesis that UCH-L1 may be a potential biomarker for DHCA-induced ischemic neuronal apoptosis.
Methods:
Anesthetized piglets were used to perform cardiopulmonary bypass (CPB). DHCA was induced for 1 hour followed by CPB rewarming. Blood samples were collected and serum UCH-L1 levels were measured. Neuron apoptosis and Bax and Bcl-2 proteins in hippocampus were examined. The relationship between neuron apoptosis and UCH-L1 level was determined by receiver operating characteristics (ROC) curves and correlation analysis.
Results:
DHCA resulted in marked neuronal apoptosis, significant increase in Bax:Bcl-2 ratio in hippocampus and UCH-L1 level elevations in serum (all P<0.05). Positive correlation was obtained between serum UCH-L1 level and the severity of neuron apoptosis (r= 0.78, P<0.01). By ROC, the area under the curve were 0.88 (95% CI: 0.74-0.99; P<0.01), 0.81 (95% CI: 0.81-0.96; P<0.05), 0.71 (95% CI: 0.47-0.92; P=0.11) for UCH-L1, Bax/Bcl-2 ratio and Bax, respectively. Using a cut-off point of 0.25, the UCH-L1 predicted neuronal apoptosis with a sensitivity of 85% and specificity of 57%.
Conclusion:
Serum UCH-L1, as an easy and quick measurable biomarker, can predict neural apoptosis induced by DHCA. The elevation in UCH-L1 concentration is consistent with the severity of neural apoptosis following DHCA.
