Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathway
Abstract Background The protective effect of Coenzyme Q10 (CoQ10) on the cardiovascular system has been reported, however, whether it can promote early recovery of cardiac function and alleviate cardiac remodeling after myocardial infarction (MI) remains to be elucidated. Whether CoQ10 may regulate...
| Main Authors: | , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2024-01-01
|
| Series: | BMC Cardiovascular Disorders |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12872-024-03729-x |
| _version_ | 1797340344038195200 |
|---|---|
| author | Wenxu Pan Guiquan Zhou Meiling Hu Gaoshan Li Mingle Zhang Hao Yang Kunyan Li Jingwei Li Ting Liu Ying Wang Jun Jin |
| author_facet | Wenxu Pan Guiquan Zhou Meiling Hu Gaoshan Li Mingle Zhang Hao Yang Kunyan Li Jingwei Li Ting Liu Ying Wang Jun Jin |
| author_sort | Wenxu Pan |
| collection | DOAJ |
| description | Abstract Background The protective effect of Coenzyme Q10 (CoQ10) on the cardiovascular system has been reported, however, whether it can promote early recovery of cardiac function and alleviate cardiac remodeling after myocardial infarction (MI) remains to be elucidated. Whether CoQ10 may regulate the macrophage-mediated pro-inflammatory response after MI and its potential mechanism are worth further exploration. Methods To determine the baseline plasma levels of CoQ10 by LC-MS/MS, healthy controls and MI patients (n = 11 each) with age- and gender-matched were randomly enrolled. Additional MI patients were consecutively enrolled and randomized into the blank control (n = 59) or CoQ10 group (n = 61). Follow-ups were performed at 1- and 3-month to assess cardiac function after percutaneous coronary intervention (PCI). In the animal study, mice were orally administered CoQ10/vehicle daily and were subjected to left anterior descending coronary artery (LAD) ligation or sham operation. Echocardiography and serum BNP measured by ELISA were analyzed to evaluate cardiac function. Masson staining and WGA staining were performed to analyze the myocardial fibrosis and cardiomyocyte hypertrophy, respectively. Immunofluorescence staining was performed to assess the infiltration of IL1β/ROS-positive macrophages into the ischemic myocardium. Flow cytometry was employed to analyze the recruitment of myeloid immune cells to the ischemic myocardium post-MI. The expression of inflammatory indicators was assessed through RNA-seq, qPCR, and western blotting (WB). Results Compared to controls, MI patients showed a plasma deficiency of CoQ10 (0.76 ± 0.31 vs. 0.46 ± 0.10 µg/ml). CoQ10 supplementation significantly promoted the recovery of cardiac function in MI patients at 1 and 3 months after PCI. In mice study, compared to vehicle-treated MI mice, CoQ10-treated MI mice showed a favorable trend in survival rate (42.85% vs. 61.90%), as well as significantly alleviated cardiac dysfunction, myocardial fibrosis, and cardiac hypertrophy. Notably, CoQ10 administration significantly suppressed the recruitment of pro-inflammatory CCR2+ macrophages into infarct myocardium and their mediated inflammatory response, partially by attenuating the activation of the NLR family pyrin domain containing 3 (NLRP3)/Interleukin-1 beta (IL1β) signaling pathway. Conclusions These findings suggest that CoQ10 can significantly promote early recovery of cardiac function after MI. CoQ10 may function by inhibiting the recruitment of CCR2+ macrophages and suppressing the activation of the NLRP3/IL1β pathway in macrophages. Trial registration Date of registration 09/04/2021 (number: ChiCTR2100045256). |
| first_indexed | 2024-03-08T10:00:44Z |
| format | Article |
| id | doaj.art-514e567c105a46d3a3a4af77551a2858 |
| institution | Directory Open Access Journal |
| issn | 1471-2261 |
| language | English |
| last_indexed | 2024-03-08T10:00:44Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cardiovascular Disorders |
| spelling | doaj.art-514e567c105a46d3a3a4af77551a28582024-01-29T10:56:06ZengBMCBMC Cardiovascular Disorders1471-22612024-01-0124111310.1186/s12872-024-03729-xCoenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathwayWenxu Pan0Guiquan Zhou1Meiling Hu2Gaoshan Li3Mingle Zhang4Hao Yang5Kunyan Li6Jingwei Li7Ting Liu8Ying Wang9Jun Jin10Department of Cardiology, The Second Affiliated Hospital of Army Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Army Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Army Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Army Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Army Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Army Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Army Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Army Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Army Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Army Medical UniversityDepartment of Cardiology, The Second Affiliated Hospital of Army Medical UniversityAbstract Background The protective effect of Coenzyme Q10 (CoQ10) on the cardiovascular system has been reported, however, whether it can promote early recovery of cardiac function and alleviate cardiac remodeling after myocardial infarction (MI) remains to be elucidated. Whether CoQ10 may regulate the macrophage-mediated pro-inflammatory response after MI and its potential mechanism are worth further exploration. Methods To determine the baseline plasma levels of CoQ10 by LC-MS/MS, healthy controls and MI patients (n = 11 each) with age- and gender-matched were randomly enrolled. Additional MI patients were consecutively enrolled and randomized into the blank control (n = 59) or CoQ10 group (n = 61). Follow-ups were performed at 1- and 3-month to assess cardiac function after percutaneous coronary intervention (PCI). In the animal study, mice were orally administered CoQ10/vehicle daily and were subjected to left anterior descending coronary artery (LAD) ligation or sham operation. Echocardiography and serum BNP measured by ELISA were analyzed to evaluate cardiac function. Masson staining and WGA staining were performed to analyze the myocardial fibrosis and cardiomyocyte hypertrophy, respectively. Immunofluorescence staining was performed to assess the infiltration of IL1β/ROS-positive macrophages into the ischemic myocardium. Flow cytometry was employed to analyze the recruitment of myeloid immune cells to the ischemic myocardium post-MI. The expression of inflammatory indicators was assessed through RNA-seq, qPCR, and western blotting (WB). Results Compared to controls, MI patients showed a plasma deficiency of CoQ10 (0.76 ± 0.31 vs. 0.46 ± 0.10 µg/ml). CoQ10 supplementation significantly promoted the recovery of cardiac function in MI patients at 1 and 3 months after PCI. In mice study, compared to vehicle-treated MI mice, CoQ10-treated MI mice showed a favorable trend in survival rate (42.85% vs. 61.90%), as well as significantly alleviated cardiac dysfunction, myocardial fibrosis, and cardiac hypertrophy. Notably, CoQ10 administration significantly suppressed the recruitment of pro-inflammatory CCR2+ macrophages into infarct myocardium and their mediated inflammatory response, partially by attenuating the activation of the NLR family pyrin domain containing 3 (NLRP3)/Interleukin-1 beta (IL1β) signaling pathway. Conclusions These findings suggest that CoQ10 can significantly promote early recovery of cardiac function after MI. CoQ10 may function by inhibiting the recruitment of CCR2+ macrophages and suppressing the activation of the NLRP3/IL1β pathway in macrophages. Trial registration Date of registration 09/04/2021 (number: ChiCTR2100045256).https://doi.org/10.1186/s12872-024-03729-xCoenzyme Q10MacrophageInflammationMyocardial infarctionInterleukin-1 beta |
| spellingShingle | Wenxu Pan Guiquan Zhou Meiling Hu Gaoshan Li Mingle Zhang Hao Yang Kunyan Li Jingwei Li Ting Liu Ying Wang Jun Jin Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathway BMC Cardiovascular Disorders Coenzyme Q10 Macrophage Inflammation Myocardial infarction Interleukin-1 beta |
| title | Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathway |
| title_full | Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathway |
| title_fullStr | Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathway |
| title_full_unstemmed | Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathway |
| title_short | Coenzyme Q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the NLRP3/IL1β pathway |
| title_sort | coenzyme q10 mitigates macrophage mediated inflammation in heart following myocardial infarction via the nlrp3 il1β pathway |
| topic | Coenzyme Q10 Macrophage Inflammation Myocardial infarction Interleukin-1 beta |
| url | https://doi.org/10.1186/s12872-024-03729-x |
| work_keys_str_mv | AT wenxupan coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway AT guiquanzhou coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway AT meilinghu coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway AT gaoshanli coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway AT minglezhang coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway AT haoyang coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway AT kunyanli coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway AT jingweili coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway AT tingliu coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway AT yingwang coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway AT junjin coenzymeq10mitigatesmacrophagemediatedinflammationinheartfollowingmyocardialinfarctionviathenlrp3il1bpathway |