Platelets activation is associated with elevated plasma mitochondrial DNA during cardiopulmonary bypass
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Published on: March 23, 2018
Chaoyi Qin1, Jun Gu1, Jia Hu1
1Department of Cardiovascular Surgery, West China Hospital, Si Chuan University, Guo Xue Alley 37, Cheng du, Sichuan, 610041, People's Republic of China.
Background:
Mitochondrial DNA (mtDNA) was reported as a pro-inflammatory agent. In our previous study, elevation of plasma mtDNA was revealed after cardiac surgery with cardiopulmonary bypass (CPB). Platelets were activated during the cardiac surgery and recent study revealed its ability to release mtDNA. Our present study postulated that the elevated plasma mtDNA comes from activated platelets, which plays a critical role in post-CPB inflammatory responses.
Methods:
Sixty-eight patients who underwent coronary artery bypass graft (CABG) with CPB were enrolled in our study. Blood samples were collected before induction of anaesthesia (T1), at the end of CPB (T2), 12 h post-CPB (T3), 24 h post-CPB (T4), 48 h post-CPB (T5) and 72 h post-CPB (T6). Blood samples were analyzed for the routine blood test and prepared for plasma isolation. MtDNA concentration was measured by rt-PCR, and TNF-α and IL-6 were examined by specific ELISA kits. Subgroup study was analyzed by activation levels of platelet. Basic information, mtDNA level, TNF-α level and IL-6 level were all carefully studied in each quartile.
Results:
Activation level of platelets increased and peaked at T2, which decreased gradually from T3 to T6 (P < 0.05). MtDNA increased after CPB, peaked at T3, and then backed from T4 to T6 (P < 0.05). Bivariate correlation between peak activation level of platelets and peak plasma mtDNA level showed a positive correlation between these two parameters (r = 0.683, P < 0.0001). Both TNF-α and IL-6 showed similar patterns as mtDNA, with an increase from T1 to T3 and a decrease from T4 to T6 (P < 0.05). Subgroup analysis further demonstrated that patients with higher activation levels of PLT had higher plasma mtDNA levels and inflammatory level (P < 0.05).
Conclusions:
Our study revealed the dynamic changes of activation level of platelets and identified the interesting association between platelets activation and plasma mtDNA, suggesting a novel potential mechanism of activated platelets-induced post-CPB inflammatory responses.
Insights
Activated platelets release mitochondrial DNA (mtDNA), contributing to inflammation after cardiac surgery with cardiopulmonary bypass (CPB). This study links platelet activation to elevated plasma mtDNA and inflammatory markers post-CPB.
Area of Science:
- Cardiovascular Surgery
- Immunology
- Molecular Biology
Background:
- Mitochondrial DNA (mtDNA) is recognized as a pro-inflammatory agent.
- Previous research indicated elevated plasma mtDNA post-cardiac surgery with cardiopulmonary bypass (CPB).
- Platelets, activated during CPB, are known to release mtDNA, suggesting their involvement in post-CPB inflammation.
Purpose of the Study:
- To investigate the role of activated platelets in releasing mitochondrial DNA (mtDNA) after cardiac surgery.
- To explore the association between platelet activation, plasma mtDNA levels, and inflammatory responses following CPB.
- To elucidate a potential mechanism for platelet-induced inflammation in the post-CPB period.
Main Methods:
- Sixty-eight patients undergoing coronary artery bypass graft (CABG) with CPB were studied.
- Blood samples were collected at multiple time points: pre-anesthesia, end of CPB, and 12, 24, 48, and 72 hours post-CPB.
- Plasma mtDNA concentrations were measured using rt-PCR, while TNF-α and IL-6 levels were assessed via ELISA. Platelet activation levels were analyzed in subgroups.
Main Results:
- Platelet activation increased post-CPB, peaking at the end of CPB (T2) and gradually decreasing thereafter.
- Plasma mtDNA levels rose post-CPB, reaching a peak at 12 hours (T3) before declining.
- A significant positive correlation was observed between peak platelet activation and peak plasma mtDNA levels (r=0.683, P<0.0001).
- Pro-inflammatory cytokines TNF-α and IL-6 mirrored the patterns of mtDNA, with higher levels in patients with greater platelet activation.
Conclusions:
- Platelet activation dynamics and plasma mtDNA levels change significantly following CPB.
- A strong association exists between platelet activation and elevated plasma mtDNA levels.
- Activated platelets represent a potential key mechanism driving inflammatory responses after CPB.
