Predictors for new-onset conduction block in patients with pure native aortic regurgitation after transcatheter aortic valve replacement with a new-generation self-expanding valve (VitaFlow Liberty™): a retrospective cohort study.

BACKGROUND: New-generation self-expanding valves can improve the success rate of transcatheter aortic valve replacement (TAVR) for severe pure native aortic regurgitation (PNAR). However, predictors of new-onset conduction block post-TAVR using new-generation self-expanding valves in patients with PNAR remain to be established. Therefore, this study aimed to identify predictors of new-onset conduction block post-TAVR using new-generation self-expanding valves (VitaFlow Liberty™) in patients with PNAR. METHODS: In this retrospective cohort study, patients were categorized into pacemaker and non-pacemaker groups based on their need for new postoperative permanent pacemaker implantation (PPI). Based on the postoperative presence of either new-onset complete left bundle branch block (cLBBB) or high-grade atrioventricular block (AVB), patients were further classified into conduction disorder and non-conduction disorder groups. Laboratory, echocardiographic, computed tomography, preoperative and postoperative electrocardiography, and procedural and clinical data were collected immediately after TAVR and during hospitalization and compared between the groups. Multivariate logistic regression analysis was performed incorporating the significant variables from the univariate analyses. RESULTS: This study examined 68 consecutive patients with severe PNAR who underwent TAVR. In 20 patients, a permanent pacemaker was fitted postoperatively. Multivariate logistic regression analysis revealed an association between the need for postoperative PPI and preoperative complete right bundle branch block (cRBBB) or first-degree AVB, as well as a non-tubular left ventricular outflow tract (LVOT). In addition, valve implantation depth and angle of aortic root were independent predictors of new-onset cLBBB or high-grade AVB developing post-TAVR. The predictive value of valve implantation depth and angle of aortic root was further supported by receiver operating characteristic curve analysis results. CONCLUSIONS: In patients with PNAR undergoing TAVR using self-expanding valves, preoperative cRBBB or first-degree AVB and a non-tubular LVOT were indicators of a higher likelihood of PPI requirement. Moreover, deeper valve implantation depth and greater angle of aortic root may be independent risk factors for new-onset cLBBB or high-grade AVB post-TAVR. Valve implantation depth and angle of aortic root values may be used to predict the possibility of new cLBBB or high-grade AVB post-TAVR.

A sudden increase in heart rate during ablation of the right superior pulmonary venous vestibule is correlated with pain-relief in patients undergoing atrial fibrillation ablation.

BACKGROUND: A sudden increase in heart rate (HR) during ablation of the right superior pulmonary venous vestibule (RSPVV) is often detected in patients undergoing circumferential pulmonary vein isolation (CPVI). In our clinical practices, we observed that some patients had few complaints of pain during the procedures under conscious sedation. AIM: We aimed to investigate whether there is a correlation between a sudden increase in HR during AF ablation of the RSPVV and pain relief under conscious sedation. METHODS: We prospectively enrolled 161 consecutive paroxysmal AF patients who underwent the first ablation from July 1, 2018, to November 30, 2021. Patients were assigned to the R group when they had a sudden increase in HR during the ablation of the RSPVV, and the others were assigned to the NR group. Atrial effective refractory period and HR were measured before and after the procedure. Visual Analogue Scale (VAS) scores, vagal response (VR) during ablation, and the amount of fentanyl used were also documented. RESULTS: Eighty-one patients were assigned to the R group, and the remaining 80 were assigned to the NR group. The post-ablation HR (86.3 ± 8.8 vs. 70.0 ± 9.4 b/min; p ≤ 0.001) was higher in the R group than in pre-ablation. Ten patients in the R group had VRs during CPVI, as well as 52 patients in the NR group. The VAS score [2.3 (1.3-3.4) vs. 6.0 (4.4-6.9); p ≤ 0.001)] and the amount of fentanyl used (107 ± 12 vs. 172 ± 26 ug; p ≤ 0.001) were significantly lower in the R group. CONCLUSION: A sudden increase in HR during the ablation of the RSPVV was correlated with pain relief in patients undergoing AF ablation under conscious sedation.

Relationship Between Prognostic Nutritional Index and New-Onset Atrial Fibrillation in Patients with Acute ST-Elevation Myocardial Infarction Following Percutaneous Coronary Intervention.

Multiple reports relate new-onset atrial fibrillation (NOAF) to poor clinical outcomes in patients with ST-elevation myocardial infarction (STEMI) who received percutaneous coronary intervention (PCI). The prognostic nutritional index (PNI) is a reliable indicator of immunonutritional-inflammatory status, and it is linked to clinical outcomes in cardiovascular disease patients. This research aims to explore the relationship between NOAF and PNI.Overall, 600 STEMI patients treated with PCI were recruited for this retrospective analysis. The patients were categorized into the NOAF group or sinus rhythm (SR) group. Logistic regression and receiver operating characteristic (ROC) curve analyses were conducted to assess PNI estimation. Lastly, the Kaplan-Meier curve was used to compare all-cause mortality between both groups.The combined NOAF incidence in PCI-treated STEMI patients was 7.7%. PNI was independently correlated with NOAF using multivariate regression analyses (odds ratio [OR], 0.824; 95% confidence interval [CI], 0.750-0.906; P < 0.001). In ROC curve analyses, the best PNI threshold value for predicting NOAF was 40.1, with sensitivity, and specificity of 76.09% and 71.30%, respectively area under the curve, 0.787; 95% CI, 0.752-0.819; P < 0.001). After a median of 41-month follow-up, the Kaplan-Meier curve revealed that the NOAF patients displayed an elevated all-cause death incidence compared with SR patients, with a log-rank of P = 0.005.This study demonstrated that PNI is an independent predictor of NOAF in STEMI patients during hospitalization after PCI, which is strongly correlated with a poor outcome upon discharge.

The relationship between IL-6 levels and the angiographic severity of coronary artery disease following percutaneous coronary intervention in acute coronary syndrome patients.

BACKGROUND: The present investigation was developed for the exploration of the association between IL-6 levels and acute coronary syndrome (ACS) findings upon angiographic evaluation. METHODS: A retrospective review of 346 patients suffering from chest discomfort that underwent coronary angiography was performed. The SYNergy between Percutaneous Coronary Intervention with TAXus and cardiac surgery (SYNTAX) score (SS) and SS II were used to gauge ACS severity, with ACS patients being stratified into two groups based on an SS value of 22 and the median SS II value. Associations between IL-6 levels and SS or SS II values were assessed through Spearman's correlation analyses, and independent predictors of intermediate-high SS or high SS II were identified via a multivariate logistic regression approach. A receiver operating characteristic (ROC) curve was employed to explore of the predictive value of IL-6 levels. RESULTS: IL-6 was positively correlated with both SS (r = 0.479, P < 0.001) and SS II (r = 0.305, P < 0.001). Moreover, IL-6 levels were independently predictive of intermediate-high SS and high SS II values. ROC curves further demonstrated that IL-6 was able to predict intermediate-high SS and high SS II, with area under the curve (AUC) values of 0.806 and 0.624, respectively. CONCLUSION: IL-6 levels are closely linked to the extent of coronary artery disease in ACS patients undergoing percutaneous coronary intervention. IL-6 levels may thus serve as a valuable and non-invasive biomarker of high-risk ACS patients.

Lung tumor presenting with acute myocardial infarction and lower extremity arterial embolism.

BACKGROUND: Lung tumor embolization leading to acute myocardial infarction (AMI) is rare. Previouscases of lung tumor embolization were reported in the coronary artery. We describe here a case of lung tumor embolization leading to the simultaneous occurrence of AMI and lower extremity arterial embolism. CASE PRESENTATION: A 64-year-old patient was admitted to the emergency department complaining of chest pain and was diagnosed with AMI.An echocardiography showed a mass in the left atrium that was speculated to be a myxoma. An emergency coronary angiography found no evidence of atherosclerosis. On the second day of admission, the patient was diagnosed with lower extremity arterial embolism. Initially, we speculated that the left atrium myxoma caused an embolism resulting in the AMI and lower extremity arterial embolism.However, a lung tumor was the real cause of both conditions. Unfortunately, the patient abandoned treatment when he learned of his disease and died three days later after being discharged from the hospital. CONCLUSIONS: Lung tumor embolism is an extremely rare cause of AMI. Even rarer is the case presented here, in which a lung tumor embolism caused AMI and lower extremity arterial embolism. Clinicians should recognize lung tumor embolism as a potential cause of AMI.

Ticagrelor alleviates sepsis-induced myocardial injury via an adenosine-dependent pathway in a mouse sepsis model.

PURPOSE: The purpose of this study was to determine whether ticagrelor, a classic anti-platelet drug, has a therapeutic effect on sepsis-induced myocardial injury. METHODS: The C57BL6J mice received oral ticagrelor (10, 25 and 50 mg/kg) for seven days after which cecum ligation and puncture (CLP) were performed. An adenosine-receptor antagonist (CGS15943) was administered two hours before CLP. After 24 h, cardiac function was measured using cardiac echocardiography, then the heart and blood were collected. Hematoxylin and eosin (HE) staining and terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL staining) were used to observe pathological changes and cardiomyocyte apoptosis. Plasma concentration of TNF-α, IL-6 and adenosine and myocardial tissue levels of TNF-α and IL-6 were determined. Survival analysis was performed. Western blot was used to determine the expression of a signalling protein in the myocardial tissue. RESULTS: The HE and TUNEL staining showed less inflammatory cell infiltration and less cardiomyocyte apoptosis in the ticagrelor group. Cardiac echocardiography showed preserved heart function in the ticagrelor group. Plasma TNF-α, IL-6 and relative expression of TNF-α and IL-6 in myocardial tissue were significantly lower in the ticagrelor group. Plasma adenosine levels were significantly higher in the ticagrelor group. Adenosine-receptor antagonists significantly blocked the protective effect of ticagrelor. Ticagrelor reduced the mortality of sepsis mice, and this reduction was blocked by the adenosine-receptor antagonist. Western blot showed that ticagrelor activated the phosphorylation of AKT and mTOR. Adenosine-receptor antagonists inhibited the activation of AKT and mTOR. CONCLUSION: The protective effect of ticagrelor was dependent on adenosine-receptor activation, with downstream upregulation of phosphorylation of AKT and mTOR.

Blocking the A2B adenosine receptor alleviates myocardial damage by inhibiting spleen-derived MDSC mobilisation after acute myocardial infarction.

BACKGROUND: Myeloid-derived suppressor cell (MDSC) mobilisation is an important immune event in acute myocardial infarction (AMI). The A2B adenosine receptor (A2BAR) plays key role in regulating MDSC function, but its specific involvement in MDSC mobilisation in AMI remains unclear. METHODS: In AMI patients, the circulating MDSC ratio and A2BAR mRNA expression were measured. A mouse AMI model was established by left anterior descending coronary artery (LADCA) ligation. MDSCs were analysed by FACS and immunofluorescence staining (of heart tissue). A2BAR mRNA expression was assessed by qRT-PCR. Myocardial injury was detected by HE staining. Myocardial cell apoptosis was analysed by immunohistochemistry. Cardiac systolic function was evaluated by transthoracic echocardiography. RESULTS: In AMI patients, the circulating MDSC ratio was increased and positively correlated with A2BAR mRNA expression (r = 0.86, p < 0.01). In AMI model mice, the percentage of MDSCs was increased in the circulation and infarcted heart and decreased in the spleen. MRS-1754-mediated A2BAR inhibition decreased the MDSC ratio in the circulation and infarcted heart and prevented the decrease in MDSC number in the spleens of mice with AMI. A2BAR blockade inhibited myocardial cell apoptosis, alleviated myocardial inflammatory injury, and improved myocardial systolic function in the AMI mouse model. Similar results were found in mice after splenectomy. Additionally, spleen-derived MDSC injection increased the MDSC ratio in the infarcted heart, increased myocardial cell apoptosis, aggravated myocardial injury, and decreased cardiac systolic function in mice with AMI. CONCLUSION: Blocking A2BAR alleviates myocardial damage and improves myocardial systolic function through inhibition of spleen-derived MDSC mobilisation after AMI. Key MessagesSpleen-derived MDSC mobilisation aggravates myocardial inflammatory injury within 24 h of AMI.A2BAR promotes spleen-derived MDSC mobilisation within 24 h of AMI.Blocking A2BAR improves myocardial systolic function through inhibition of spleen-derived MDSC mobilisation.

Triglyceride-Glucose Index and New-Onset Atrial Fibrillation in ST-Segment Elevation Myocardial Infarction Patients After Percutaneous Coronary Intervention.

Background: New-onset atrial fibrillation (NOAF) is associated with worse prognostic outcomes in cases diagnosed with ST-segment elevation myocardial infarction (STEMI) patients after percutaneous coronary intervention (PCI). The triglyceride-glucose (TyG) index, as a credible and convenient marker of insulin resistance, has been shown to be predictive of outcomes for STEMI patients following revascularization. The association between TyG index and NOAF among STEMI patients following PCI, however, has not been established to date. Objective: To assess the utility of the TyG index as a predictor of NOAF incidence in STEMI patients following PCI, and to assess the relationship between NOAF and long-term all-cause mortality. Methods: This retrospective cohort research enrolled 549 STEMI patients that had undergone PCI, with these patients being clustered into the NOAF group and sinus rhythm (SR) group. The predictive relevance of TyG index was evaluated through logistic regression analyses and the receiver operating characteristic (ROC) curve. Kaplan-Meier curve was employed to explore differences in the long-term all-cause mortality between the NOAF and SR group. Results: NOAF occurred in 7.7% of the enrolled STEMI patients after PCI. After multivariate logistic regression analysis, the TyG index was found to be an independent predictor of NOAF [odds ratio (OR): 8.884, 95% confidence interval (CI): 1.570-50.265, P = 0.014], with ROC curve analyses further supporting the predictive value of this parameter, which exhibited an area under ROC curve of 0.758 (95% CI: 0.720-0.793, P < 0.001). All-cause mortality rates were greater for patients in the NOAF group in comparison with the SR group over a median 35-month follow-up period (log-rank P = 0.002). Conclusions: The TyG index exhibits values as an independent predictor of NOAF during hospitalization, which indicated a poorer prognosis after a relatively long-term follow-up.

Triggering receptor expressed on myeloid cells-2 promotes survival of cardiomyocytes after myocardial ischemic injury through PI3K/AKT pathway.

Background: Previous studies have already revealed that triggering receptor expressed on myeloid cells-2 (TREM2) plays a significant protective role during the pathogenesis of ischemia injury in both brain and liver. This study aims to investigate the effect of TREM2 in myocardial ischemic injury. Methods: The mice myocardial infarction (MI) model was established via left anterior descending coronary artery ligation. TREM2 expression was examined with RT-PCR and Western blot. Whereafter, mice were randomly divided into control, sham, MI, Ad.TREM2 transfection group and Ad.Null transfection group. Recombinant adenovirus containing the gene coding full-length mouse TREM2 and EGFP (Ad.TREM2) or control vector containing EGFP gene only (Ad.Null) were immediately intramyocardial injected after left anterior descending ligated. After 7 days of MI, HE, Masson and TUNEL staining were performed to find the myocardial injury, infarcted size and cell apoptosis. Besides, echocardiography was performed to determine cardiac function. In addition, Western blot was performed to check the activity of PI3K/AKT signaling pathway in myocardial tissue. Furthermore, the plasma concentrations of TREM2 in 19 coronary artery disease (CAD) patients and 8 healthy controls were measured. Results: Compared with the sham group, TREM2 expression was significantly up-regulated in cardiac tissue in mice with MI. Cardiac tissue in mice transfected with Ad.TREM2 was demonstrated with alleviated injury, reduced infarct size, and decreased number of apoptotic cells. Echocardiography revealed that heart function was significantly improved in Ad.TREM2 transfection mice. Also, TREM2 transfection significantly activated the phosphorylation of AKT. At last, the plasma concentration of TREM2 was significantly elevated in patients with CAD and correlated with the severity of CAD. Conclusions: TREM2 may curb myocardial ischemia injury via activating PI3K/AKT signal pathway. Besides, plasma TREM2 may be treated as a potential biomarker in the diagnosis of CAD to reflect the severity of coronary stenosis.

A rare cause of abdominal pain managed unconventionally: acute renal infarction caused by atrial fibrillation: a case report.

BACKGROUND: Atrial fibrillation is one of the most common arrhythmias. The main thrombotic complication of arterial fibrillation is ischemic stroke, but it can also cause acute renal infarction from embolization. The low incidence and nonspecific clinical manifestations of acute renal infarction make it difficult to diagnose, often leading to either delayed diagnosis or misdiagnosis. Due to its rarity, more efficient treatment guidelines are helpful for the management of acute renal infarction related to the thromboembolic complication of arterial fibrillation. CASE REPORTS: We report a case of acute renal infarction due to underlying arterial fibrillation, where a novel interventional therapeutic method was used. A 66-year-old Chinese man with arterial fibrillation, not on anticoagulation due to the patient's preference, and coronary artery disease post-percutaneous coronary intervention to left anterior descending artery about 1 year ago, was currently on dual antiplatelet therapy. He suddenly developed intermittent and sharp left-sided abdominal pain and was found to have an acute left renal infarction on computed tomography scan. Angiogram showed acute occlusion of the left renal artery due to thromboembolism. For this patient, a combination method of local thrombus aspiration, angioplasty, and infusion of nitroglycerin and diltiazem were used, restoring blood flow to the left kidney. After recovery, the patient was discharged on aspirin, clopidogrel, and warfarin. At 6 months follow-up, there was no residual kidney dysfunction. CONCLUSIONS: Acute renal infarction from thromboembolism is a rare but serious complication of arterial fibrillation. More efficient and different options for intervention methods will benefit the treatment of this disease. Here, we report a combination therapeutic method that has not been used in acute renal infarction associated with arterial fibrillation, and which restored renal perfusion and prevented long-term kidney injury.

Analysis of gut microbiota in patients with acute myocardial infarction by 16S rRNA sequencing.

Background: An increasing number of studies have shown that gut microbiota are associated with human cardiovascular disease, but the characteristics of intestinal flora in patients with acute myocardial infarction (AMI) are still unclear. In this study, we aimed to investigate the difference of intestinal microflora between patients with AMI and healthy people, and to find the effect of percutaneous coronary intervention (PCI) on intestinal microflora. Methods: A total of 60 stool samples and 60 peripheral blood samples were collected from 20 previously diagnosed AMI patients and 20 healthy people serving as controls. Gut microbiota communities were analyzed via 16 ribosomal RNA-sequencing (16S rRNA). Gut microbiota-derived metabolites, trimethylamine N-oxide (TMAO) and short-chain fatty acids (SCFA), in the blood were detected using stable isotope dilution high-performance liquid chromatography with on line electrospray ionization tandem mass spectrometry (LC/MS/MS). Results: The results showed that a distinct pattern of gut microbiota was observed in AMI patients compared to healthy controls. AMI patients had lower microbiological richness but no significant change in diversity. Bacteroidetes and Verrucomicobia showed an upward trend, whereas Proteobacteria showed a downward trend in AMI patients. During a longitudinal study to compare the changes in bacteria before and after treatment, we found routine cardiac admission therapy 1 week after PCI surgery had no effect on the microbial community structure in patients. There were significantly higher levels of plasma TMAO in AMI patients' microbiota than that in the control group. Contrarily, there was no obvious change in SCFA. Conclusions: The gut microbiota of patients with AMI differs from that of normal people, and the metabolic products of microflora are more abundant in the plasma of AMI than control cases. Microflora may act on the cardiovascular system through metabolites, and regulation of the microfloral structure may be used in the future treatment of cardiovascular diseases.

The Relationship between Red Cell Distribution Width and Residual SYNTAX Scores in ST-Segment Elevation Myocardial Infarction Patients after Percutaneous Coronary Intervention.

OBJECTIVE: Residual SYNTAX score (rSS) values have been suggested to serve as an independent predictor of mortality in ST-segment elevation myocardial infarction (STEMI) patients following percutaneous coronary intervention (PCI). Prior work has also indicated that red cell distribution width (RDW) can predict the incidence of major adverse cardiac events (MACEs) in STEMI patients. As such, we sought to explore the relationship between RDW and rSS in STEMI patients that have undergone PCI. METHODS: In total, 456 eligible patients were recruited for this study. Youden's index was used to calculate the optimal RDW cut-off value, after which the relationship between RDW and rSS values was assessed through Spearman's correlation analyses. Independent predictors of high rSS levels were then identified via multivariate logistic regression analysis. RESULTS: Patients were separated into two groups based upon whether they exhibited high RDW levels (>13.9, Group 1) or low RDW levels (<13.9, Group 2). The average rSS value of patients in Group 2 was found to be significantly decreased compared to patients in Group 1 (P < 0.001). RDW values were found to be positively correlated with rSS (r = 0.604, P < 0.001), and multivariate logistic regression analysis determined that high RDW levels were independently predictive of higher rSS (OR = 27.1 [14.8-51.7]; P < 0.001). Additionally, a nomogram incorporating RDW exhibited good calibration, discriminative capacity, and clinical utility. CONCLUSIONS: In summary, RDW is strongly correlated with rSS in STEMI patients following PCI, with high RDW levels serving as an independent predictor of high rSS in this patient population.

Relationship between Plasma Lipoprotein-Associated Phospholipase A2 Concentrations and Apolipoprotein in Stable Coronary Artery Disease Patients.

BACKGROUND: Increasing evidence states that the plasma lipoprotein-associated phospholipase A2 (Lp-PLA2) levels and apolipoprotein particles are regarded as the risk maker for cardiovascular heart disease. Nevertheless, the issue about whether Lp-PLA2 is associated with apolipoprotein particles in individuals who have been diagnosed as stable coronary artery disease (CAD) remains largely unexplored. METHOD: All 569 participants engaged in this research, who never took lipid-lowering drugs, had been divided into groups by the coronary angiography (CAG), namely, stable CAD: n = 291; non-CAD: n = 278. The results concerning Lp-PLA2 levels were calculated by Elisa Kit, while apolipoprotein particles were measured by the department of laboratory. RESULTS: The plasma concentration of Lp-PLA2 was remarkably higher in stable CAD group than the non-CAD group (136.0 ± 60.5 ng/mL vs. 113.2 ± 65.6 ng/mL, P < 0.001). Pearson correlation analyses explained the plasma Lp-PLA2 concentration was correlated with apoB (r = 0.390, P < 0.001) and apoB/apoA1 (r = 0.450, P < 0.001), not associated with apoA1 (r = -0.099, P = 0.101). Conversely, the association remains unobserved among non-CAD patients except apoA1. Moreover, multiple linear regression revealed the relations between Lp-PLA2 concentrations and apoB (ß = 0.390, P < 0.001), as well as apoB/apoA1 (ß = 0.450, P < 0.001), but not apoA1 (ß = -0.099, P = 0.121). After adjustment for several risk factors regarding CAD, like hypertension, gender, smoking, age, and diabetes mellitus, there had still been positive associations between the Lp-PLA2 concentration and apoB (ß = 0.364, P < 0.001), as well as apoB/apoA1 (ß = 0.390, P < 0.001). CONCLUSION: The plasma levels of Lp-PLA2 provide positively a key link with apoB, apoB/apoA-1 among stable CAD, denoting the communication between Lp-PLA2 and apolipoprotein particles in the state of CAD.

High glucose induced endothelial cell reactive oxygen species via OGG1/PKC/NADPH oxidase pathway.

AIMS: Reactive oxygen species (ROS) caused by high glucose (HG) is involved in a lot of diseases including diabetes. However, the underlying mechanism of ROS induction by HG remains unclear. Emerging evidence has shown the 8-oxoguanine glycosylase (OGG1) is the main DNA glycosylase responsible for atherosclerosis, obesity, hepatic steatosis, and insulin resistance, and so on. Our aim was to explore the role of OGG1 on HG-mediated endothelial ROS. MAIN METHODS: Human umbilical vein endothelial cells (HUVECs) were exposed to HG (30 mM) for different time periods. HG predominantly inhibited OGG1 expression in a time-dependent manner measured by western blotting, qPCR and immunofluorescence. Additionally, HUVECs were cultured with a fluorescent probe, DCFH and DHE, after being subjected to HG. Cell chemiluminescence and flow cytometry results revealed that HG caused endothelial ROS activation. KEY FINDINGS: High glucose remarkably decreased endothelial OGG1 expression. The overexpression of OGG1 significantly reversed HG-mediated PKC and NADPH oxidase activities and ROS levels. Moreover, manipulated expression of PKC significantly contacted the role of OGG1 on NADPH oxidase activation. SIGNIFICANCE: These results suggest that OGG1 downregulation promoted HG-induced endothelial ROS production and might be a potential clinical treatment target of diabetics.

The mobilization of splenic reservoir myeloid-derived suppressor cells in sepsis-induced myocardial injury.

BACKGROUND: Myeloid-derived suppressor cells (MDSCs) play key roles in sepsis, but whether the bone marrow is considered the only source remains unclear. The current knowledge about the mechanism of MDSCs leading to myocardial injury in sepsis is poor. METHODS: In sepsis patients with cardiac dysfunction, the circulating percentage of CD14-CD11b+ and serum concentrations of IL-6 and IL-1ß were measured. A mouse sepsis model was established through caecum ligation and puncture (CLP). Animals were divided into four groups: control, sham, CLP and CLP+splenectomy (CLPS). Serum concentrations of IL-6, IL-1ß, TnI and NT-proBNP were measured. CD11b+Gr-1+ cells were detected by immunofluorescence staining and RT-PCR. Myocardial injury was detected by HE, Masson and TUNEL staining. The expression of mTOR, P53 and caspase-3 was measured by Western blot. RESULTS: In sepsis patients, circulating MDSCs were increased, and the serum concentrations of IL-6 and IL-1ß were elevated. The serum concentrations of IL-6 and IL-1ß were correlated with the ratio of circulating MDSCs. In the mouse sepsis model, the spleen was the major source of CD11b+Gr-1+ cells that migrated into circulation and the heart in sepsis. The serum concentrations of IL-6 and IL-1ß were also elevated. Echocardiography and serum biomarkers showed that cardiomyocyte damage and cardiac hypofunction in sepsis-induced myocardial injury. The expression of CD11b, Gr-1 and pro-inflammatory cytokines in the heart was significantly higher in sepsis patients than that in controls. Pathological staining and TUNEL staining showed obvious myocardial damage and cell apoptosis. The Western blot analysis indicated that in the heart, the activation of mTOR was inhibited and that the expression of P53 and caspase-3 was elevated in sepsis-induced myocardial injury. CONCLUSION: In sepsis-induced myocardial injury, splenic reservoir CD11b+Gr-1+ cells rapidly migrated into circulation and the heart, further impairing heart function via the high expression of P53 through the inhibition of mTOR.

Expression of B2 Receptor on Circulating CD34-Positive Cells and Outcomes of Myocardial Infarction.

BACKGROUND: Bradykinin B2 receptor (B2R) is a widely expressed cell surface receptor. The relationship between B2R expression on circulating CD34+ cells and prognosis of myocardial infarction remains unknown. METHODS: We analyzed the expression of B2R on circulating CD34-positive cells and plasma VEGF concentration in 174 myocardial infarction patients. All involved patients were divided into two groups: high B2R group and low B2R group according to the median B2R expression percentage. 48 months of follow-up was performed. The endpoints were heart failure and revascularization. RESULTS: The plasma level of VEGF in the low B2R group is 67 ± 12 pg/mL, whereas the high B2R group has significantly elevated VEGF levels of 145 ± 27 pg/mL (P < 0.001). The concentration of VEGF has correlated with expression of B2R (r = 0.574, P < 0.001). During the 48 months of follow-up, low expression of B2 receptor on circulating CD34-positive cells indicates the high incidence of heart failure (hazard ratio: 2.247; 95% confidence interval: 1.110-4.547; P = 0.024) and revascularization (hazard ratio: 2.335; 95% confidence interval: 1.075-5.074; P = 0.032). Kaplan-Meier survival analysis showed that the cumulative hazard of heart failure (P = 0.014) and revascularization (P = 0.032) has significant differences between low B2R and high B2R. CONCLUSION: Low expression of B2R on circulating progenitor cells indicated the poor outcomes of myocardial infarction.