Chinese Society of Cardiology guidelines on the diagnosis and treatment of adult fulminant myocarditis.

Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium. It is characterized by acute onset, rapid progress and high risk of death. Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm. According to China's practical experience, the adoption of the "life support-based comprehensive treatment regimen" (with mechanical circulation support and immunomodulation therapy as the core) can significantly improve the survival rate and long-term prognosis. Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.

Emergency Treatment and Photoacoustic Assessment of Spinal Cord Injury Using Reversible Dual-Signal Transform-Based Selenium Antioxidant.

Spinal cord injury (SCI), following explosive oxidative stress, causes an abrupt and irreversible pathological deterioration of the central nervous system. Thus, preventing secondary injuries caused by reactive oxygen species (ROS), as well as monitoring and assessing the recovery from SCI are critical for the emergency treatment of SCI. Herein, an emergency treatment strategy is developed for SCI based on the selenium (Se) matrix antioxidant system to effectively inhibit oxidative stress-induced damage and simultaneously real-time evaluate the severity of SCI using a reversible dual-photoacoustic signal (680 and 750 nm). Within the emergency treatment and photoacoustic severity assessment (ETPSA) strategy, the designed Se loaded boron dipyrromethene dye with a double hydroxyl group (Se@BDP-DOH) is simultaneously used as a sensitive reporter group and an excellent antioxidant for effectively eliminating explosive oxidative stress. Se@BDP-DOH is found to promote the recovery of both spinal cord tissue and locomotor function in mice with SCI. Furthermore, ETPSA strategy synergistically enhanced ROS consumption via the caveolin 1 (Cav 1)-related pathways, as confirmed upon treatment with Cav 1 siRNA. Therefore, the ETPSA strategy is a potential tool for improving emergency treatment and photoacoustic assessment of SCI.

Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice.

OBJECTIVE: Inflammation and oxidative stress contribute to the progression of sepsis-induced acute lung injury (ALI). SAM domain, SH3 domain and nuclear localization signals 1 (SAMSN1) is a signaling adaptor protein, and mainly regulates inflammatory response of various immune cells. The present study generates macrophage-specific SAMSN1-knockout (Samsn1MKO) and SAMSN1-transgenic (Samsn1MTG) mice to investigate its role and mechanism in sepsis-induced ALI. METHODS: Samsn1MKO and Samsn1MTG mice were exposed to lipopolysaccharide (LPS) instillation or cecal ligation and puncture (CLP) surgery to induce sepsis-induced ALI. Bone marrow transplantation, cellular depletion and non-invasive adoptive transfer of bone marrow-derived macrophages (BMDMs) were performed to validate the role of macrophage SAMSN1 in sepsis-induced ALI in vivo. Meanwhile, BMDMs were isolated from Samsn1MKO or Samsn1MTG mice to further clarify the role of SAMSN1 in vitro. RESULTS: Macrophage SAMSN1 expression was increased in response to LPS stimulation, and negatively correlated with LPS-induced ALI in mice. Macrophage SAMSN1 deficiency exacerbated, while macrophage SAMSN1 overexpression ameliorated LPS-induced inflammation, oxidative stress and ALI in mice and in BMDMs. Mechanistically, we found that macrophage SAMSN1 overexpression prevented LPS-induced ALI though activating AMP-activated protein kinase α2 (AMPKα2) in vivo and in vitro. Further studies revealed that SAMSN1 directly bound to growth factor receptor bound protein 2-associated protein 1 (GAB1) to prevent its protein degradation, and subsequently enhanced protein kinase A (PKA)/AMPKα2 activation in a protein tyrosine phosphatase, non-receptor type 11 (PTPN11, also known as SHP2)-dependent manner. Moreover, we observed that macrophage SAMSN1 overexpression diminished CLP-induced ALI in mice. CONCLUSION: Our study documents the protective role of macrophage SAMSN1 against sepsis-induced inflammation, oxidative stress and ALI through activating AMPKα2 in a GAB1/SHP2/PKA pathway, and defines it as a promising biomarker and therapeutic target to treat sepsis-induced ALI.

CircSAMD4A aggravates H/R-induced cardiomyocyte apoptosis and inflammatory response by sponging miR-138-5p.

Hypoxia/reoxygenation (H/R)-induced myocardial cell injury is the main cause of acute myocardial infarction (AMI). Many proofs show that circular RNA plays an important role in the development of AMI. The purpose of this study was to investigate the role of circSAMD4A in H/R-induced myocardial injury. The levels of circular SAMD4A (circSAMD4A) were detected in the heart tissues of AMI mice and H/R-induced H9C2 cells, and the circSAMD4A was suppressed in AMI mice and H/R-induced H9C2 cells to investigate its' function in AMI. The levels of circSAMD4A and miR-138-5p were detected by real-time quantitative PCR, and MTT assay was used to detect cell viability. TUNEL analysis and Annexin V-FITC were used to determine apoptosis. The expression of Bcl-2 and Bax proteins was detected by Western blot. IL-1ß, TNF-α and IL-6 were detected by ELISA kits. The study found that the levels of circSAMD4A were up-regulated after H/R induction and inhibition of circSAMD4A expression would reduce the H/R-induced apoptosis and inflammation. MiR-138-5p was down-regulated in H/R-induced H9C2 cells. circSAMD4A was a targeted regulator of miR-138-5p. CircSAMD4A inhibited the expression of miR-138-5p to promote H/R-induced myocardial cell injury in vitro and vivo. In conclusion, CircSAMD4A can sponge miR-138-5p to promote H/R-induced apoptosis and inflammatory response.

Extracorporeal Membrane Oxygenation in Severe Acute Respiratory Distress Syndrome Caused by Chlamydia psittaci: A Case Report and Review of the Literature.

Background: Infection of Chlamydia psittaci (C. psittaci) could lead to serious clinical manifestations in humans, including severe pneumonia with rapid progression, adult respiratory distress syndrome (ARDS), sepsis, multiple organ dysfunction syndromes (MODS), and probably death. Implementation of extracorporeal membrane oxygenation (ECMO) in the patient with severe ARDS gives a promising new method for recovery. Case Presentation: We report our successful use of venovenous (VV) ECMO in a 48-year-old man who manifested with severe respiratory distress syndrome, acute kidney injury, and septic shock caused by a diagnosis of pneumonia. After the combination of therapy including anti-infection, mechanical ventilation, and continuous renal replacement therapy (CRRT), acute inflammatory syndrome developed. However, his respiratory status rapidly deteriorated. Then, venoarterial (VA)-ECMO support was placed on the patient as suddenly slowing of the heart rate. Harlequin (North-South) syndrome occurred after ECMO initiation. A series of the process could not relieve hypoxia in the upper body. At last, transition to VV-ECMO improved hypoxia. The duration of VV-ECMO was 7 days and the mechanical ventilation was weaned on the next day. On the day of ECMO weaning, nanopore targeted sequencing (NTS) of bronchoalveolar lavage fluid (BALF) reported the presence of C. psittaci. After 19 days of critical systemic rehabilitation and combination therapy, the patient fully recovered from C. psittaci. Conclusion: This is the first reported case of the patient receiving ECMO for C. psittaci pneumonia. ECMO puts the lungs on temporary rest, promotes the recovery of pulmonary function, and also wins time for finding the pathogens, which is crucial in the treatment of rare pathogens.

The Role of Gut Microbiota in Tumor Immunotherapy.

Tumor immunotherapy is the fourth therapy after surgery, chemotherapy, and radiotherapy. It has made great breakthroughs in the treatment of some epithelial tumors and hematological tumors. However, its adverse reactions are common or even more serious, and the response rate in some solid tumors is not satisfactory. With the maturity of genomics and metabolomics technologies, the effect of intestinal microbiota in tumor development and treatment has gradually been recognized. The microbiota may affect tumor immunity by regulating the host immune system and tumor microenvironment. Some bacteria help fight tumors by activating immunity, while some bacteria mediate immunosuppression to help cancer cells escape from the immune system. More and more studies have revealed that the effects and complications of tumor immunotherapy are related to the composition of the gut microbiota. The composition of the intestinal microbiota that is sensitive to treatment or prone to adverse reactions has certain characteristics. These characteristics may be used as biomarkers to predict the prognosis of immunotherapy and may also be developed as "immune potentiators" to assist immunotherapy. Some clinical and preclinical studies have proved that microbial intervention, including microbial transplantation, can improve the sensitivity of immunotherapy or reduce adverse reactions to a certain extent. With the development of gene editing technology and nanotechnology, the design and development of engineered bacteria that contribute to immunotherapy has become a new research hotspot. Based on the relationship between the intestinal microbiota and immunotherapy, the correct mining of microbial information and the development of reasonable and feasible microbial intervention methods are expected to optimize tumor immunotherapy to a large extent and bring new breakthroughs in tumor treatment.

Normothermic ex vivo Heart Perfusion Combined With Melatonin Enhances Myocardial Protection in Rat Donation After Circulatory Death Hearts via Inhibiting NLRP3 Inflammasome-Mediated Pyroptosis.

OBJECTIVE: The adoption of hearts from donation after circulatory death (DCD) is a promising approach for the shortage of suitable organs in heart transplantation. However, DCD hearts suffer from serious ischemia/reperfusion injury (IRI). Recent studies demonstrate that nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome-mediated pyroptosis is a novel target to ameliorate myocardial IRI. Melatonin is shown to inhibit NLRP3 inflammasome-mediated pyroptosis. Therefore, this study is designed to verify the hypothesis that melatonin can protect the heart graft preserved with ex vivo heart perfusion (EVHP) against myocardial IRI via inhibiting NLRP3 inflammasome-mediated pyroptosis in a rat model of DCD. METHODS: Donor-heart rats were randomly divided into three groups: (1) Control group: non-DCD hearts were harvested from heart-beating rats and immediately preserved with allogenic blood-based perfusate at constant flow for 105 min in the normothermic EVHP system; (2) DCD-vehicle group; and (3) DCD-melatonin group: rats were subjected to the DCD procedure with 25 min of warm ischemia injury and preserved by the normothermic EVHP system for 105 min. Melatonin (200 µmol/L) or vehicle was perfused in the cardioplegia and throughout the whole EVHP period. Cardiac functional assessment was performed every 30 min during EVHP. The level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis of heart grafts submitted to EVHP were evaluated. RESULTS: Twenty five-minute warm ischemia injury resulted in a significant decrease in the developed pressure (DP), dP/dt max , and dP/dt min of left ventricular of the DCD hearts, while the treatment with melatonin significantly increased the DP, dP/dt max of the left ventricular of DCD hearts compared with DCD-vehicle group. Furthermore, warm ischemia injury led to a significant increase in the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis in the hearts preserved with EVHP. However, melatonin added in the cardioplegia and throughout the EVHP period significantly attenuated the level of oxidative stress, inflammatory response, apoptosis, and NLRP3 inflammasome-mediated pyroptosis compared with DCD-vehicle group. CONCLUSION: EVHP combined with melatonin post-conditioning attenuates myocardial IRI in DCD hearts by inhibiting NLRP3 inflammasome-mediated pyroptosis, which might expand the donor pool by the adoption of transplantable DCD hearts.

Artificial Intelligence for Clinical Decision Support in Sepsis.

Sepsis is one of the main causes of death in critically ill patients. Despite the continuous development of medical technology in recent years, its morbidity and mortality are still high. This is mainly related to the delay in starting treatment and non-adherence of clinical guidelines. Artificial intelligence (AI) is an evolving field in medicine, which has been used to develop a variety of innovative Clinical Decision Support Systems. It has shown great potential in predicting the clinical condition of patients and assisting in clinical decision-making. AI-derived algorithms can be applied to multiple stages of sepsis, such as early prediction, prognosis assessment, mortality prediction, and optimal management. This review describes the latest literature on AI for clinical decision support in sepsis, and outlines the application of AI in the prediction, diagnosis, subphenotyping, prognosis assessment, and clinical management of sepsis. In addition, we discussed the challenges of implementing and accepting this non-traditional methodology for clinical purposes.

Circular RNA circANKRD36 regulates Casz1 by targeting miR-599 to prevent osteoarthritis chondrocyte apoptosis and inflammation.

Osteoarthritis (OA) is an ageing-related disease characterized by articular cartilage degradation and joint inflammation. circRNA has been known to involve in the regulation of multiple inflammatory diseases including OA. However, the mechanism underlying how circRNA regulates OA remains to be elucidated. Here, we report circANKRD36 prevents OA chondrocyte apoptosis and inflammation by targeting miR-599, which specifically degrades Casz1. We performed circRNA sequencing in normal and OA tissues and found the expression of circANKRD36 is decreased in OA tissues. circANKRD36 is also reduced in IL-1ß-treated human chondrocytes. FACS analysis and Western blot showed that the knockdown of circANKRD36 promotes the apoptosis and inflammation of chondrocytes in IL-1ß stress. We then found miR-599 to be the target of circANKRD36 and correlate well with circANKRD36 both in vitro and in vivo. By database analysis and luciferase assay, Casz1 was found to be the direct target of miR-599. Casz1 helps to prevent apoptosis and inflammation of chondrocytes in response to IL-1ß. In conclusion, our results proved circANKRD36 sponge miR-599 to up-regulate the expression of Casz1 and thus prevent apoptosis and inflammation in OA.

miR-199a-5p Exacerbated Intestinal Barrier Dysfunction through Inhibiting Surfactant Protein D and Activating NF-κB Pathway in Sepsis.

Sepsis is a severe disease, which results from the excessive inflammatory response to the infection. Dysfunction of intestinal barrier is a crucial problem in various pathological conditions. Meanwhile, microRNAs exhibit significant roles in the modulation of many diseases, including sepsis. Multiple investigations indicate that miR-199a-5p participates in different human diseases. Nevertheless, little is known on the roles of miR-199a-5p in sepsis. Herein, we evaluated the mechanism of miR-199a-5p on the intestinal barrier dysfunction in sepsis. Intestinal mucosa permeability indicators including D-lactic acid, DAO, and FD-40 levels were determined, and they were greatly increased in sepsis. Then, we proved that miR-199a-5p was induced in sepsis mice tissues and isolated intestinal epithelial cells. Moreover, miR-199a-5p increased D-lactic acid, DAO, and FD-40 while inhibition of miR-199a-5p exhibited a reversed process. Additionally, we observed that miR-199a-5p affected the oxidative damage and inflammation in the intestine tissues from sepsis mice. The content of MDA was elevated whereas SOD was remarkably repressed in the miR-199a-5p mimic group. IL-6, IL-1ß, and TNF-α were induced by miR-199a-5p overexpression while IL-10 was reduced by miR-199a-5p. Subsequently, surfactant protein D (SP-D) was predicted as the target of miR-199a-5p. The activation of NF-κB has been identified in sepsis. Herein, we demonstrated that inhibitor of miR-199a-5p contributed to IEC injury via targeting SP-D and inactivating the NF-κB pathway. These revealed miR-199a-5p exacerbated the intestinal barrier dysfunction via inhibiting SP-D and activating the NF-κB pathway in sepsis.

MEG3 Alleviated LPS-Induced Intestinal Injury in Sepsis by Modulating miR-129-5p and Surfactant Protein D.

Sepsis and intestinal injury triggered by sepsis are common in intensive care units, which can contribute to a high mortality. lncRNAs can modulate gene expression, and they are closely involved in multiple diseases, including sepsis. In our present study, we investigated the biological function of MEG3 in sepsis, especially during the intestinal injury. Currently, we observed that in LPS-induced sepsis mouse models, the intestinal injury was triggered. Meanwhile, we reported that MEG3 was greatly decreased in vivo, with an increase of miR-129-5p and inhibition of SP-D. Then, MEG3 was overexpressed, and we found that its overexpression repressed the intestinal injury via downregulating miR-129-5p in sepsis mice. Moreover, TNF-α and IL-6 expression was elevated in intestinal tissues compared to the control groups. MEG3 restrained the activation of TNF-α and IL-6, in sepsis models. Subsequently, to induce the inflammatory injury of sepsis, human colorectal Caco2 cells were treated with 10 ng/ml LPS. 10 ng/ml LPS significantly inhibited Caco2 cell proliferation and increased the apoptosis. Additionally, MEG3 was decreased whereas miR-129-5p was obviously increased in Caco2 cells incubated with LPS. Interestingly, we showed that MEG3 repressed cell apoptosis partly and enhanced Caco2 cell proliferation. miR-129-5p overexpression could reverse the effect of MEG3 in vitro. Previously, we proved SP-D was reduced in sepsis and it depressed the intestinal injury in vivo. Finally, the correlation among MEG3, miR-129-5p, and SP-D was predicted and confirmed in our investigation. These findings indicated that MEG3 might be a potential target for intestinal damage caused by sepsis via regulating miR-129-5p and SP-D.

Application of CRISPR/Cas9 technology in sepsis research.

CRISPR/Cas9, as a new genome-editing tool, offers new approaches to understand and treat diseases, which is being rapidly applied in various areas of biomedical research including sepsis field. The type II prokaryotic CRISPR/Cas system uses a single-guide RNA (sgRNA) to target the Cas9 nuclease to a specific genomic sequence, which is introduced into disease models for functional characterization and for testing of therapeutic strategies. This incredibly precise technology can be used for therapeutic research of gene-related diseases and to program any sequence in a target cell. Most importantly, the multifunctional capacity of this technology allows simultaneous editing of several genes. In this review, we focus on the basic principles, advantages and limitations of CRISPR/Cas9 and the use of the CRISPR/Cas9 system as a powerful tool in sepsis research and as a new strategy for the treatment of sepsis.

MicroRNA-21 Contributes to Acute Liver Injury in LPS-Induced Sepsis Mice by Inhibiting PPARα Expression.

The severity of sepsis may be associated with excessive inflammation, thus leading to acute liver injury. MicroRNA-21 is highly expressed in the liver of a variety of inflammation-related diseases, and PPARα is also proved to participate in regulating inflammation. In the present study, the LPS-induced sepsis model was established. We found that microRNA-21 expression was upregulated in the liver of sepsis mice, and microRNA-21 inhibition significantly reduced the liver injury. The expression of liver injury markers, inflammation cytokines, and PPARα in the septic mice was higher than in antagomir-21 treated septic mice. In addition, we also found that PPARα is the target gene of microRNA-21; PPARα antagonist GW6471 could reverse the effect of antagomir-21. In conclusion, our study illustrated that microRNA-21 exacerbate acute liver injury in sepsis mice by inhibiting PPARα expression.

PTPN2 negatively regulates macrophage inflammation in atherosclerosis.

Atherosclerosis is the main cause of cardiovascular disease. Systemic inflammation is one important characteristic in atherosclerosis. Pro-inflammatory macrophages can secrete inflammatory factors and promote the inflammation of atherosclerosis. It has a great value for the treatment of atherosclerosis by inhibiting the release of inflammatory factors in macrophages. However, the detailed mechanism of this process is still unclear. In this study, we constructed an APOE-/- mice model of atherosclerosis to research the molecular mechanism of atherosclerosis. Protein tyrosine phosphatase non-receptor type 2 (PTPN2), an anti-inflammatory gene, was dramatically decreased in inflammatory mice. Deletion of PTPN2 could significantly induce monocytes toward M1 phenotype of macrophages, enhance the secretion of IL-12 and IL-1, and promote cell proliferation, invasion and metastasis. Mechanism research showed that PTPN2-mediated p65/p38/STAT3 de-phosphorylation could block the process of macrophage inflammation. In vivo experiments showed that PTPN2 may effectively inhibit the inflammatory response during atherosclerosis. In conclusion, we uncovered the negative role of PTPN2 in the occurrence of atherosclerosis, and this study provides a new potential target for atherosclerosis treatment.

miR-182-5p contributes to intestinal injury in a murine model of Staphylococcus aureus pneumonia-induced sepsis via targeting surfactant protein D.

Sepsis is a severe clinical disease, which is resulted from the excessive host inflammation response to the infection. Growing evidence indicates that Staphylococcus aureus pneumonia is a significant cause of sepsis, which can lead to intestinal injury, inflammation, and apoptosis. Studies have shown that miR-182-5p can serve as a tumor oncogene or a tumor suppressive microRNA in various cancers, however, its biological role in sepsis is still uninvestigated. Here, we reported that miR-182-5p was obviously increased in S. aureus pneumonia mice models. Loss of miR-182-5p inhibited intestinal damage and intestinal apoptosis as indicated by the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. In addition, we observed the lack of miR-182-5p altered the local inflammatory response to pneumonia in the intestine. Elevated tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were observed in intestinal tissue of pneumonia groups compared with the shams. Furthermore, miR-182-5p knockout (KO) pneumonia group demonstrated decreased levels of intestinal TNF-α and IL-6. Primary murine intestinal epithelial cells were isolated and cultured in our investigation. We exhibited downregulation of miR-182-5p repressed intestinal epithelial cells apoptosis and rescued the cell viability. Meanwhile, miR-182-5p caused elevated cell apoptosis and reduced cell proliferation. Moreover, the surfactant protein D (SP-D) binds with the bacterial pathogens and remove the pathogens and apoptotic bodies, which exhibits important roles in modulating immune responses. It was displayed in our study that SP-D was greatly decreased in pneumonia mice models. SP-D was predicted as a downstream target of miR-182-5p. These data concluded that miR-182-5p promoted intestinal injury in S. aureus pneumonia-induced sepsis via targeting SP-D.

NEAT1 promotes myocardial ischemia-reperfusion injury via activating the MAPK signaling pathway.

Myocardial ischemia-reperfusion (IR) injury is a common cardiovascular problem, which remains a major cause of death in the world. Emerging evidence has suggested that long noncoding RNAs are crucial players in myocardial injury. However, the functional involvement of nuclear enriched abundant transcript 1 (NEAT1) in myocardial IR injury remains poorly investigated. Our study focused on the mechanism of NEAT1 in myocardial IR injury. Here, we reported a crucial role for NEAT1 in exacerbating cardiac IR injury. NEAT1 was greatly increased in myocardial IR injury mice models. As exhibited knockdown of NEAT1 resulted in attenuated myocardial IR injury in vivo. In addition, we found that NEAT1 was dramatically induced by hypoxia/reoxygenation in H9c2 cells. Lactate dehydrogenase (LDH), malondialdehyde, reactive oxygen species levels, and endoplasmic reticulum stress-regulated cardiomyocyte apoptosis were inhibited by the downregulation of NEAT1. Here, it was shown that knockdown of NEAT1 was able to repress tumor necrosis factor-α, interleukin-1ß, and IL-6 expression. The silence of NEAT1 protected against IR injury via decreasing troponin levels, cardiocytes apoptosis, creatine kinase, and lactate LDH release in vivo. Meanwhile, the mitogen-activated protein kinase (MAPK) signaling was involved in NEAT1-mediated myocardial IR injury. In summary, our data indicated that NEAT1 contributed to myocardial IR injury via activating the MAPK pathway.

Iron-load exacerbates the severity of atherosclerosis via inducing inflammation and enhancing the glycolysis in macrophages.

Atherosclerosis is still the major cause of morbidity and mortality all over the world. Recently, it has been reported increased levels of tissue iron increase the risk of atherosclerosis. However, the detailed mechanism of iron-induced atherosclerosis progression is barely known. Here, we used apoE-deficient mice models to investigate the effects of low iron diet (<0 mg iron carbonyl/kg), high iron diet (25,000 mg iron carbonyl/kg) on atherosclerosis in vivo. As exhibited, we observed that CD68 was significant enriched by high iron diet in apoE-deficient mice. In addition, transforming growth factor ß, tumor necrosis factor α, interleukin 6 (IL-6), IL-23, IL-10, and IL-1ß levels were also greatly induced by high iron diet. Then, we found that the iron load promoted the inflammation response in macrophages. Moreover, macrophage polarization is a process by which macrophage can express various functional programs in activating macrophages. Here, we observed that iron-load macrophages were polarized toward a proinflammatory macrophage phenotype. The polarization of M1 macrophage was promoted by ferric ammonium citrate (FAC) in bone marrow derived macrophages (BMDMs). Furthermore, ECAR and cellular OCR in BMDM with or without FAC was examined. As shown, BMDM indicated with 50 µM FAC showed a significant increase in basic state and maximal ECAR in contrast to the control group. However, there was no significant difference in OCR. This indicated that the glycolysis was involved in the polarization of M1 macrophage triggered by iron-load. In conclusion, we indicated that the iron load exacerbates the progression of atherosclerosis via inducing inflammation and enhancing glycolysis in macrophages.