Serum levels of lipoprotein-associated phospholipase A2 are associated with coronary atherosclerotic plaque progression in diabetic and non-diabetic patients.

BACKGROUND: Lp-PLA2 is linked to cardiovascular diseases and poor outcomes, especially in diabetes, as it functions as a pro-inflammatory and oxidative mediator. OBJECTIVES: This research aimed to explore if there is a connection between the serum levels of Lp-PLA2 and the progression of coronary plaques (PP) in individuals with type 2 diabetes mellitus (T2DM) and those without the condition. MATERIALS AND METHODS: Serum Lp-PLA2 levels were measured in 137 T2DM patients with PP and 137 T2DM patients with no PP, and in 205 non-diabetic patients with PP and 205 non-diabetic patients with no PP. These individuals met the criteria for eligibility and underwent quantitative coronary angiography at the outset and again after about one year of follow-up. The attributes and parameters of the participants at the outset were recorded. RESULTS: Increased serum levels of Lp-PLA2 were closely associated with coronary artery PP, and also significantly correlated with change of MLD, change of diameter stenosis and change of cumulative coronary obstruction in both diabetic and non-diabetic groups, with higher correlation coefficients in diabetic patients as compared with non-diabetic patients. Moreover, multivariate logistic regression analysis showed that serum Lp-PLA2 level was an independent determinant of PP in both groups, with OR values more significant in diabetic patients than in non-diabetic patients. CONCLUSIONS: Levels of serum Lp-PLA2 show a significant association with the progression of coronary atherosclerotic plaque in patients with T2DM and those without, especially among individuals with diabetes.

[Environmental Benefits of Pollution and Carbon Reduction by Bus Fleet Electrification in Zhengzhou].

Electrification of bus fleets is an effective approach to reducing transportation-related pollution and carbon emissions. Evaluating the impact of electrification on existing bus fleets can provide valuable insights for promoting full electrification of public transportation in large cities. Utilizing the fuel life cycle method, we analyzed the CO2 and pollutant emissions of Zhengzhou's bus fleet before and after electrification and evaluated emissions under different electrification scenarios. Our results indicated that after electrification, the fuel life cycle CO2 and PM2.5 emissions increased by 32.6% and 42.6%, respectively, whereas CO, NOx, and VOC emissions decreased by 28%, 34%, and 25%, respectively. Optimizing the power generation structure is a critical factor in reducing CO2 and PM2.5 emissions during the electrification process. The best scenario for comprehensive electrification and power generation structure optimization could result in a 38.7% reduction in CO2, as well as reductions of 80.1% in CO, 84.4% in NOx, 92.2% in VOC, and 30.2% in PM2.5. Prioritizing electrification on long-distance routes is recommended during the replacement process. Additionally, replacing plug-in hybrid natural gas vehicles with pure electric vehicles has both advantages and disadvantages in terms of emission reduction. Achieving pollution reduction and carbon synergies requires advancing fleet replacement and power structure adjustments simultaneously.

Day-night pattern of acute ST-segment elevation myocardial infarction onset in patients with obstructive sleep apnea.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) is associated with acute nocturnal hemodynamic and neurohormonal abnormalities that may increase the risk of coronary events, especially during the nighttime. This study sought to investigate the day-night pattern of acute ST-segment elevation myocardial infarction (STEMI) onset in patients with OSA and its impact on cardiovascular adverse events. METHODS: We prospectively enrolled 397 patients with STEMI, for which the time of onset of chest pain was clearly identified. All participants were categorized into non-OSA (n = 280) and OSA (n = 117) groups. The association between STEMI onset time and major adverse cardiovascular and cerebrovascular events was estimated by Cox proportional hazards regression. RESULTS: STEMI onset occurred from midnight to 5:59 am in 33% of patients with OSA, as compared with 15% in non-OSA patients (P < .01). For individuals with OSA, the relative risk of STEMI from midnight to 5:59 am was 2.717 [95% confidence interval (CI) 1.616 - 4.568] compared with non-OSA patients. After a median of 2.89 ± 0.78 years follow-up, symptom onset time was found to be significantly associated with risk of major adverse cardiovascular and cerebrovascular events in patients with OSA, while there was no significant association observed in non-OSA patients. Compared with STEMI presenting during noon to 5:59 pm, the hazard ratios for major adverse cardiovascular and cerebrovascular events in patients with OSA were 4.683 (95% CI 2.024 - 21.409, P = .027) for midnight to 5:59 am and 6.964 (95% CI 1.379 - 35.169, P = .019) for 6 pm to midnight, whereas the hazard ratios for non-OSA patients were 1.053 (95% CI 0.394 - 2.813, P = .917) for midnight to 5:59 am and 0.745 (95% CI 0.278 - 1.995, P = .558) for 6 pm to midnight. CONCLUSIONS: Patients with OSA exhibited a peak incidence of STEMI between midnight and 5:59 am, which showed an independent association with cardiovascular adverse events. CITATION: Wang Y, Buayiximu K, Zhu T, et al. Day-night pattern of acute ST-segment elevation myocardial infarction onset in patients with obstructive sleep apnea. J Clin Sleep Med. 2024;20(5):765-775.

Predictive value of early left ventricular end-diastolic volume changes for late left ventricular remodeling after ST-elevation myocardial infarction.

BACKGROUD: Left ventricular remodeling (LVR) is a major predictor of adverse outcomes in patients with acute ST-elevation myocardial infarction (STEMI). This study aimed to prospectively evaluate LVR in patients with STEMI who were successfully treated with primary percutaneous coronary intervention (PCI) and examine the relationship between early left ventricular dilation and late LVR. METHODS: Overall 301 consecutive patients with STEMI who underwent primary PCI were included. Serial echocardiography was performed on the first day after PCI, on the day of discharge, at 1 month, and 6 months after discharge. RESULTS: Left ventricular remodeling occurred in 57 (18.9%) patients during follow-up. Left ventricular end-diastolic volume (LVEDV) reduced from day 1 postoperative to discharge in the LVR group compared with that in the non-LVR (n-LVR) group. The rates of change in LVEDV (ΔLVEDV%) were -5.24 ± 16.02% and 5.05 ± 16.92%, respectively (p < 0.001). LVEDV increased in patients with LVR compared with n-LVR at 1-month and 6-month follow-ups (ΔLVEDV% 13.05 ± 14.89% vs. -1.9 ± 12.03%; 26.46 ± 14.05% vs. -3.42 ± 10.77%, p < 0.001). Receiver operating characteristic analysis showed that early changes in LVEDV, including ΔLVEDV% at discharge and 1-month postoperative, predicted late LVR with an area under the curve value of 0.80 (95% confidence interval 0.74-0.87, p < 0.0001). CONCLUSIONS: Decreased LVEDV at discharge and increased LVEDV at 1-month follow-up were both associated with late LVR at 6-month. Comprehensive and early monitoring of LVEDV changes may help to predict LVR.

Hypoxia-associated genes predicting future risk of myocardial infarction: a GEO database-based study.

Background: Patients with unstable angina (UA) are prone to myocardial infarction (MI) after an attack, yet the altered molecular expression profile therein remains unclear. The current work aims to identify the characteristic hypoxia-related genes associated with UA/MI and to develop a predictive model of hypoxia-related genes for the progression of UA to MI. Methods and results: Gene expression profiles were obtained from the GEO database. Then, differential expression analysis and the WGCNA method were performed to select characteristic genes related to hypoxia. Subsequently, all 10 hypoxia-related genes were screened using the Lasso regression model and a classification model was established. The area under the ROC curve of 1 shows its excellent classification performance and is confirmed on the validation set. In parallel, we construct a nomogram based on these genes, showing the risk of MI in patients with UA. Patients with UA and MI had their immunological status determined using CIBERSORT. These 10 genes were primarily linked to B cells and some inflammatory cells, according to correlation analysis. Conclusion: Overall, GWAS identified that the CSTF2F UA/MI risk gene promotes atherosclerosis, which provides the basis for the design of innovative cardiovascular drugs by targeting CSTF2F.

Association of Serum BAFF Levels with Cardiovascular Events in ST-Segment Elevation Myocardial Infarction.

OBJECTIVES: The B cell activating factor (BAFF) is a B cell survival factor involved in atherosclerosis and ischemia-reperfusion (IR) injury. This study sought to investigate whether BAFF is a potential predictor of poor outcomes in patients with ST-segment elevation myocardial infarction (STEMI). METHODS: We prospectively enrolled 299 patients with STEMI, and serum levels of BAFF were measured. All subjects were followed for three years. The primary endpoint was major adverse cardiovascular events (MACEs), including cardiovascular death, nonfatal reinfarction, hospitalization for heart failure (HF), and stroke. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of BAFF for MACEs. RESULTS: In multivariate analysis, BAFF was independently associated with risk of MACEs (adjusted HR 1.525, 95% CI 1.085-2.145; p = 0.015) and cardiovascular death (adjusted hazard ratio [HR] 3.632, 95% confidence interval [CI] 1.132-11.650, p = 0.030) after adjustment for traditional risk factors. Kaplan-Meier survival curves demonstrated that patients with BAFF levels above the cut-off value (1.46 ng/mL) were more likely to have MACEs (log-rank p < 0.0001) and cardiovascular death (log-rank p < 0.0001). In subgroup analysis, the impact of high BAFF on MACEs development was stronger in patients without dyslipidemia. Furthermore, the C-statistic and Integrated Discrimination Improvement (IDI) values for MACEs were improved with BAFF as an independent risk factor or when combined with cardiac troponin I. CONCLUSIONS: This study suggests that higher BAFF levels in the acute phase are an independent predictor of the incidence of MACEs in patients with STEMI.

Evaluating traffic emission control policies based on large-scale and real-time data: A case study in central China.

The traffic control policies, including "Odd and Even" (OAE) and "One Day Per Week" (ODPW), were adopted in Zhengzhou, China. In this study, we use the bottom-up policy evaluation framework to capture the temporal-spatial characteristics of traffic conditions and vehicle emissions under various traffic restriction scenarios. Moreover, we use the street-scale simulation model to evaluate the effectiveness of improving air quality. Results showed that the improvements in traffic conditions led to the emission decrease by about 28.3 % for carbon monoxide (CO), 16.2 % for nitrogen oxide (NOx), 21.3 % for particulate matter (PM2.5), and 23.2 % for total hydrocarbon (THC) under OAE. During ODPW, total vehicle emissions decreased by 14.1 % for CO, 10.2 % for NOx, 13.7 % for PM2.5, and 12.4 % for THC. However, the spatial analysis indicates traffic restrictions could not significantly reduce those emissions caused by high traffic volume; besides, buses, middle-duty trucks, and heavy-duty trucks have partly offset the reduction benefit from restrictions. The air quality simulation results reveal no significant concentration decrease of CO and nitrogen dioxide (NO2) in most areas. With the update of vehicles, stricter management of high-emission vehicles, and limited coverage for implementation of policies, the traffic control policies were not as effective as before. The limitations of the restriction policies are gradually prominent, and upgrade policies are urgently needed to continuously improve urban air quality in the future.

Apolipoprotein B Displays Superior Predictive Value Than Other Lipids for Long-Term Prognosis in Coronary Atherosclerosis Patients and Particular Subpopulations: A Retrospective Study.

PURPOSE: Accumulating evidence that apolipoprotein B (apoB) plays a critical role in predicting coronary heart disease (CHD) and future outcomes. The 2019 European Society of Cardiology/European Atherosclerosis Society guidelines suggest that apoB can be an alternative to non-HDL-C or LDL-C in patients with high triglyceride levels, diabetes, obesity, metabolic syndrome, or very low LDL-C levels. This study explores whether apoB can also serve as predictive value for long-term major adverse cardiovascular events (MACEs) in normal people and specific coronary atherosclerosis patients. METHODS: A total of 826 patients were followed up over 10 years, and the risk factors for MACEs were retrospectively analyzed in patients with CHD and particular subpopulations. All statistical analyses were performed in R software. Cox regressions were performed to assess independent risk factors of long-term MACEs in the atherosclerosis group and CHD subgroups. Kaplan-Meier survival curves were used to evaluate the survival rate for patients in different apoB quartiles, and receiver-operating characteristic curves were used to compare apoB and other lipids in predicting the presence of long-term MACE. FINDINGS: apoB could be a "risk-enhancing factor" in patients with coronary atherosclerosis disease, whereas in the Normal population, LDL-C still acted as a major risk factor for predicting MACEs. apoB was a good risk predictor for long-term cardiovascular events in coronary atherosclerosis (AS) patients, including the AS group and CHD subpopulations (including CHD + triglyceride ≥2.3 mmol/L, CHD + diabetes mellitus, CHD + body mass index ≥25 kg/m2, or CHD + metabolic syndrome). In patients with CHD whose condition was complicated with diabetes, obesity, and metabolic syndrome, apoB performed better than other lipids in predicting the presence of myocardial infarction, hospitalization due to angina, and cardiac death. Despite achieving optimal LDL-C or non-HDL-C levels, patients with CHD are still at risk of worse survival if they are unable to reach a low apoB level (lower cut points such as 65 mg/dL). IMPLICATIONS: More attention should be paid to special populations with residual elevations of atherogenic particle numbers, and greater focus should be placed on lowering baseline apoB to achieve long-term benefits. However, given that this was an observational study, the association of baseline apoB level and long-term MACEs only was evaluated; it is unclear whether the emergence of MACEs would be influenced by the dynamic changes of apoB. Because this was a retrospective and observational analysis, bias in data analysis was unavoidable; thus, the results cannot be used to generalize implications to broader patient populations, and more large-scale clinical trials are required to verify these findings. (Clin Ther. 2022;44:1071-1092) © 2022 Elsevier HS Journals, Inc.

Prognostic Value of Circulating MG53 Levels in Acute Myocardial Infarction.

Background: Mitsugumin 53 (MG53), a muscle-specific protein belonging to the TRIM family, has been demonstrated to protect the heart against oxidative injury. Although previous studies indicated that ischemic hearts released MG53 into circulation in mice, its effects in humans remains unknown. We aimed to evaluate the prognostic value of MG53 in patients with ST-segment elevation myocardial infarction (STEMI). Methods: Serum levels of MG53 were measured in 300 patients with STEMI, all patients were followed for 3 years. The primary endpoint was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular (CV) death, heart failure causing-rehospitalization, recurrent myocardial infarction (MI), and stroke. Results: Patients with a higher concentration of serum MG53 tended to be older, with a history of diabetes. MG53 levels were also highly associated with indicators reflecting heart function, such as left ventricular ejection fraction (LVEF), N terminal pro B type natriuretic peptide (NT-pro-BNP), and cardiac troponin I (cTnI) at baseline. Kaplan-Meier survival curves demonstrated that patients with MG53 levels above the cutoff value (132.17 pg/ml) were more likely to have MACEs. Moreover, it was found to be a significant predictor of CV death (HR: 6.12; 95% CI: 2.10-17.86; p = 0.001). Furthermore, the C-statistic and Integrated Discrimination Improvement (IDI) values for MACEs were improved with MG53 as an independent risk factor or when combined with cTnI. Conclusions: MG53 is a valuable prognostic marker of MACE in patients with AMI, independent of established conventional risk factors, highlighting the significance of MG53 in risk stratification post-MI.

[Emission Characteristics and Risk Assessment of Volatile Organic Compounds from Typical Factories in Zhengzhou].

To understand the characteristics and potential hazards of volatile organic compounds (VOCs) emitted from different industrial factories in Zhengzhou, several representative factories have been selected for sample collection using canisters; the samples were subsequently analyzed by GC-MS/FID system, from which the composition and risk of VOCs are discussed in this study. It was found that OVOCs, especially ethyl acetate and isopropanol, were the most important species originating from printing factories, which accounted for more than 93.1% of total VOCs. The major components related to manufacturing industries, including automobile, furniture, and coating, were aromatics, mainly m/p-xylene, o-xylene, and ethylbenzene, which contributed 33.5%-90.0% to VOCs. Halogenated hydrocarbons made the largest contribution (52.3%) to VOCs in the food processing industry. The main components of VOCs were halogenoalkanes (25.5%) and alkanes (28.8%) in rubber factories. As for graphite carbon factories, the main components of VOCs were aromatics (28.5%) and alkanes (24.1%). Compared with previous studies, the VOC emission characteristics of factories involving solvent usage in Zhengzhou are consistent with those in other cities, but the compositional information of VOCs varies across different factories, even within the same industry, due to the different production processes and raw materials used. Risk assessment showed that the concentration of VOCs emitted from solvent factories are positively correlated with ozone formation potential (OFP) and the hazard index (HI). Specifically, benzene, toluene, ethylbenzene, xylene, and other C6-C8 aromatic hydrocarbons contributed significantly to OFP and HI. The HI values were 1.18 and 2.74 in automobile manufacturing factory NO.3 and wooden furniture factory NO.5, respectively, which were higher than the limits stated by EPA regulations because of the different production processes and raw materials, and the VOCs of the factories were mainly composed of aromatics; in particular, C6-C9 benzene series contributed significantly to HI and OFP. Therefore, it is necessary to control VOCs originating from industries involving solvent usage.

Serum MG53/TRIM72 Is Associated With the Presence and Severity of Coronary Artery Disease and Acute Myocardial Infarction.

Background: Mitsugumin 53 or Tripartite motif 72 (MG53/TRIM72), a myokine/cardiokine belonging to the tripartite motif family, can protect the heart from ischemic injury and regulate lipid metabolism in rodents. However, its biological function in humans remains unclear. This study sought to investigate the relationship between circulating MG53 levels and coronary artery disease (CAD). Methods: The concentration of MG53 was measured by enzyme-linked immunosorbent assay (ELISA) in serum samples from 639 patients who underwent angiography, including 205 controls, 222 patients with stable CAD, and 212 patients with acute myocardial infarction (AMI). Logistic and linear regression analyses were used to analyze the relationship between MG53 and CAD. Results: MG53 levels were increased in patients with stable CAD and were highest in patients with AMI. Additionally, patients with comorbidities, such as chronic kidney disease (CKD) and diabetes also had a higher concentration of MG53. We found that MG53 is a significant diagnostic marker of CAD and AMI, as analyzed by logistic regression models. Multivariate linear regression models revealed that serum MG53 was significantly corelated positively with SYNTAX scores. Global Registry of Acute Coronary Events (GRACE) scores also correlated with serum MG53 levels, indicating that MG53 levels were associated with the severity of CAD and AMI after adjusting for multiple risk factors and clinical biomarkers. Conclusion: MG53 is a valuable diagnostic marker whose serum levels correlate with the presence and severity of stable CAD and AMI, and may represent a novel biomarker for diagnosing CAD and indicating the severity of CAD.

A comparative study of TR Band and a new hemostatic compression device after transradial coronary catheterization.

Objective: Transradial coronary catheterization has proved to be safe and effective in clinical practice. Various hemostatic compressive devices have been used in subsequent procedures. The objective of this study was to compare the efficacy and safety of a new hemostatic compression device and the widely used TR Band. Methods: A total of 118 patients were divided randomly into two groups: TR Band and the new hemostatic compression device. Efficacy of hemostasis, patient comfort, local vascular dysfunction, and radial artery occlusion (RAO) were evaluated and compared between groups. Results: Occurrence of errhysis or hematoma did not significantly differ between groups (13.6% vs. 11.9%, P = 0.782). Fewer patients had moderate to severe pain or moderate to severe numbness in the new hemostatic compression device group (1.7% vs. 22.0%; 1.7% vs. 18.6%, respectively). Pulse loss between distal artery and device was lower in the new hemostatic compression device group (5.1% vs. 22.0%, P = 0.007), and fewer patients experienced obstruction of venous reflux compared with the TR Band group (6.8% vs. 25.4%, P = 0.006). Combined incidence of RAO at discharge was 7.6%, and was lower in the new hemostatic compression device group (1.7% vs. 13.6%, P = 0.015). In contrast to the TR Band, application of the new hemostatic compression device was independently associated with lower incidence of RAO at discharge (odds ratio: 0.062, 95% confidence interval: 0.006-0.675, P = 0.022). Conclusions: Both the new hemostatic compression device and the TR Band can efficiently achieve hemostasis following transradial coronary catheterization. However, fewer patients felt discomfort with application of the new hemostatic compression device. Pulse loss in the artery distal to the compression device, obstruction of venous reflux, and RAO occurred significantly less often with application of the new device.

p-Cresyl sulfate promotes the formation of atherosclerotic lesions and induces plaque instability by targeting vascular smooth muscle cells.

Coronary atherosclerosis is a major complication of chronic kidney disease. This condition contributes to the increased mortality in dialysis patients. p-Cresyl sulfate (PCS) is a prototype of protein-bound uremic toxins that cannot be efficiently removed through routine dialysis procedures. In the present study, ApoE(-/-) mice that underwent 5/6 nephrectomy were randomly divided into two groups, namely, vehicle-treated group (n = 20) and PCS-treated group (n = 20). Mice were sacrificed for en face and immunohistological analyses after 8 or 24 weeks of high-fat diet. Rat aortic vascular smooth muscle cells (VSMCs) were treated with phosphate buffer solution or 500 µmol/L PCS for in vitro evaluation. PCS-treated mice were observed to suffer increased atherosclerotic lesions after eight weeks of PCS administration. Moreover, 24 weeks of PCS administration also markedly increased the vulnerability index of aortic plaques. PCS was also observed to facilitate the migration and proliferation of VSMCs during the progression of the disease. Moreover, PCS disturbed the balance between matrix metalloproteinases and tissue inhibitor of metalloproteinases within the plaques. Thus, PCS played a vital role in promoting atherogenesis and disturbing the stability of formed plaques probably by targeting VSMCs.

Atorvastatin attenuates p­cresyl sulfate­induced atherogenesis and plaque instability in ApoE knockout mice.

p-cresyl sulfate (PCS) is a protein-bound uremic toxin retained in the blood of patients with chronic kidney disease (CKD) As atherosclerosis is a primary cardiovascular complication for patients with CKD, the aim of the present study was to investigate the mechanisms underlying the aggravation of atherosclerosis by PCS. In addition, the effect of atorvastatin was assessed in reversing the effects of PCS. PCS was revealed to promote the initiation and progression of atherosclerosis. Following treatment with atorvastatin, apolipoprotein E knockout mice demonstrated a reduction in PCS­induced atherogenesis and plaque vulnerability. In addition, atorvastatin decreased the protein expression levels of vascular cell adhesion molecule­1 and intercellular cell adhesion molecule­1, and the interaction between leukocytes and endothelia. The plasma lipid profiles of mice were not significantly affected by gavage of low­dose atorvastatin. The results of the present study indicate that PCS promotes plaque growth and instability by enhancing leukocyte­endothelium interaction, and that these effects may be attenuated by atorvastatin treatment.

Safety and efficacy of a novel iopromide-based paclitaxel-eluting balloon following bare metal stent implantation in rabbit aorta abdominalis.

BACKGROUND: Drug-eluting balloons (DEB) may be promising technology for treating atherosclerotic arterial disease. In fact, several DEBs have been clinically available for the treatment of coronary in-stent restenosis (ISR), de novo coronary lesions, and peripheral artery disease. OBJECTIVE: We sought to elucidate the mechanism of action and in vivo safety and efficacy of a novel iopromide-based paclitaxel-eluting balloon. METHODS: In vitro cytotoxicity of a novel DEB on human umbilical vein endothelial cells (HUVECs) and in vivo pharmacokinetics of DEB in a rabbit aorta abdominalis were assessed. Then, bare metal stents (BMS) were implanted at both the proximal and distal sites of the rabbit aorta abdominalis. Stented vascular segments were immediately dilated with a bare balloon (control group) or the DEB (DEB group) randomly. Histological evaluation was performed in all treated segments at 28 days. Because paclitaxel is a tubulin-disrupting agent that binds preferentially to ß-tubulin, we measured ß-tubulin expression in aortal stent specimens via immunohistochemistry. RESULTS: We observed that DEB was compatible and could reduce neointimal hyperplasia compared with the bare balloon. Meanwhile, immunohistochemistry revealed that ß-tubulin expression in the DEB group increased compared with the control group, indirectly suggesting successful uptake of paclitaxel by vessel walls after DEB dilation. CONCLUSIONS: The novel DEB is safe and has a favorable vascular healing response on neointimal hyperplasia.

p-Cresyl sulfate aggravates cardiac dysfunction associated with chronic kidney disease by enhancing apoptosis of cardiomyocytes.

BACKGROUND: Cardiovascular disease is the leading cause of death in patients with chronic kidney disease. A body of evidence suggests that p-cresyl sulfate (PCS), a uremic toxin, is associated with the cardiovascular mortality rate of patients with chronic kidney disease; however, the molecular mechanisms underlying this feature have not yet been fully elucidated. METHODS AND RESULTS: We aimed to determine whether PCS accumulation could adversely affect cardiac dysfunction via direct cytotoxicity to cardiomyocytes. In mice that underwent 5/6 nephrectomy, PCS promoted cardiac apoptosis and affected the ratio of left ventricular transmitral early peak flow velocity to left ventricular transmitral late peak flow velocity (the E/A ratio) observed by echocardiography (n=8 in each group). Apocynin, an inhibitor of NADPH oxidase activity, attenuates this alteration of the E/A ratio (n=6 in each group). PCS also exhibited proapoptotic properties in H9c2 cells by upregulating the expression of p22(phox) and p47(phox), NADPH oxidase subunits, and the production of reactive oxygen species. Apocynin and N-acetylcysteine were both able to suppress the effect of PCS, underscoring the importance of NADPH oxidase activation for the mechanism of action. CONCLUSIONS: This study demonstrated that the cardiac toxicity of PCS is at least partially attributed to induced NADPH oxidase activity and reactive oxygen species production facilitating cardiac apoptosis and resulting in diastolic dysfunction.

In vivo kinetics of the uremic toxin p-cresyl sulfate in mice with variable renal function.

Uremic toxins such as p-cresyl sulfate (PCS) are associated with increased mortality for chronic kidney disease (CKD) patients, but in vivo PCS toxicity studies are limited due to the lack of a standard animal model. To establish such a model, we measured the pharmacokinetics of PCS in mice with variable renal function. Male Balb/c mice subjected to 5/6 nephrectomy (CRF), unilateral nephrectomy (UNX), or no surgery (controls) were given PCS (po, 50 mg/kg). Blood samples were collected over time and plasma PCS concentrations were measured. Over 4 h, PCS was significantly higher in the plasma of CRF mice (63.28 ± 2.76 mg/L), compared to UNX mice (3.11 ± 0.64 mg/L) and controls (0.39 ± 0.12 mg/L). The PCS half-life was greatest in CRF mice (12.07 ± 0.12 h), compared to 0.79 ± 0.04 h in UNX mice and 0.48 ± 0.02 h in control mice. However, the potential presence of additional uremic toxins along with PCS in CRF mice and rapid PCS clearance in control mice suggest that the UNX mouse would be a better PCS model to study toxicity.

Triptolide inhibits rat vascular smooth muscle cell proliferation and cell cycle progression via attenuation of ERK1/2 and Rb phosphorylation.

BACKGROUND: Drug-eluting stents have demonstrated a substantial reduction of restenosis and currently are gaining a leading position in the intervention field. Triptolide, a purified extract from Chinese herb medicine Tripterygium wilfordii hook F, exhibits antiproliferative and pro-apoptotic function in vitro and in vivo. In the present study, we investigated effects of triptolide on in-stent restenosis in vivo and in vitro, and study the biological mechanism of this drug. METHODS: Rat aortic smooth muscle cells were cultured and treated with different concentration of triptolide (0, 1, 10, and 50nM). For cell viability, we used trypan blue exclusion (TBE) survival assay. Flow cytometry was used to study the influence of triptolide on VSMCs cell cycle. Signal proteins were detected by western blotting analysis. Triptolide coated stents had been implanted in the iliac arteries of New Zealand rabbits. After 4weeks, the stented iliac artery segments were processed for embedding, staining and histomorphometric analysis. RESULTS: Triptolide of concentration 10nM, 50nM significantly inhibited fetal calf serum-induced VSMC proliferation (p<0.05). The accumulation of triptolide-treated cells at the G1/S-interphase was dose dependent. Triptolide completely blocked the cell cycle progression at 50nM. Western blotting analysis showed decreased ERK1/2 MAP kinase phosphorylation level, significantly increased p21(cip1) expression and reduced retinoblastoma protein (pRb) phosphorylation after 24h of triptolide treatment. 4weeks after the surgery, the arterial wall morphology was shown that triptolide-coated stent has less neointimal vs bare metal stent. CONCLUSIONS: Our study indicates that triptolide exert inhibitory effect on VSMC proliferation, inactivation of MAPK pathway and modulation of cell cycle proteins p21(cip1) and Rb are relating mechanisms. Triptolide drug-eluting stents attenuated neointimal formation after stent implantation in rabbit vessel. We believe that triptolide may potentially be useful in treating cardiovascular restenosis after PCI.

Long term clinical outcomes in patients with moderate renal insufficiency undergoing stent based percutaneous coronary intervention.

BACKGROUND: Patients with end-stage renal disease have a high mortality from coronary artery disease, but the impact of moderate renal insufficiency on clinical outcomes after percutaneous coronary intervention (PCI) and the effect of drug-eluting stent implantation in these patients remain unclear. This study determined the long-term effect of moderate renal insufficiency on death and major adverse cardiac events (MACE) after stent based PCI and examined whether drug-eluting stent implantation could favourably influence clinical outcome. METHODS: Major adverse cardiac events and causes of mortality were determined for 1012 patients undergoing percutaneous intervention from January 1, 2002 to December 31, 2004 at Shanghai Ruijin Hospital. Based on estimated creatinine clearance levels, long term outcomes were compared between patients with estimated creatinine clearance < 60 ml/min (renal insufficiency group; n = 410) and those with estimated creatinine clearance > or = 60 ml/min (control group; n = 602). Subgroup analysis was also made for patients with renal insufficiency between drug eluting stent (n = 264) and bare metal stent implantation (n = 146) during PCI. RESULTS: During follow-up (average 17 months) after successful PCI, all causes of death (7.1% vs 2.3%, P < 0.01) and cardiac death (3.4% vs 1.0%, all P < 0.01) were significantly higher in renal insufficiency group than in control group. For patients with moderate renal insufficiency, drug-eluting stent implantation reduced significantly all causes of death (5.3% vs 10.9%, P < 0.05) and occurrence of major cardiac adverse events (15.1% vs 24.6%, P < 0.05) compared with bare metal stents. CONCLUSIONS: Moderate renal insufficiency is an important clinical factor influencing the mortality after PCI in patients with coronary artery disease and the use of drug-eluting stents should be the preferred therapy for the improvement of long-term outcomes in such patients.

The genome of Nanoarchaeum equitans: insights into early archaeal evolution and derived parasitism.

The hyperthermophile Nanoarchaeum equitans is an obligate symbiont growing in coculture with the crenarchaeon Ignicoccus. Ribosomal protein and rRNA-based phylogenies place its branching point early in the archaeal lineage, representing the new archaeal kingdom Nanoarchaeota. The N. equitans genome (490,885 base pairs) encodes the machinery for information processing and repair, but lacks genes for lipid, cofactor, amino acid, or nucleotide biosyntheses. It is the smallest microbial genome sequenced to date, and also one of the most compact, with 95% of the DNA predicted to encode proteins or stable RNAs. Its limited biosynthetic and catabolic capacity indicates that N. equitans' symbiotic relationship to Ignicoccus is parasitic, making it the only known archaeal parasite. Unlike the small genomes of bacterial parasites that are undergoing reductive evolution, N. equitans has few pseudogenes or extensive regions of noncoding DNA. This organism represents a basal archaeal lineage and has a highly reduced genome.