Influencing factors of vascular endothelial function in patients with non-obstructive coronary atherosclerosis: a 1-year observational study.

BACKGROUND: Endothelial dysfunction may play a key role in non-obstructive coronary artery atherosclerosis. Our study aimed to evaluate the vascular endothelial function and its influencing factors in patients with non-obstructive coronary artery atherosclerosis. METHODS: A total of 131 consecutive patients with non-obstructive coronary artery atherosclerosis were enrolled. Flow-mediated dilatation (FMD) was measured at baseline and 1-year follow-up. Endothelial progenitor cells (EPCs) were counted by staining the fasting venous blood with antibodies against CD34 and vascular endothelial growth factor receptor 2. RESULTS: Systolic blood pressure, pulse pressure and the levels of HbA1c in participants with baseline FMD < 6% (n = 65) were significantly higher than those with baseline FMD ≥ 6% (n = 66). Baseline FMD was negatively associated with EPC counts (r = - 0.199, P < 0.05) and systolic blood pressure (r = - 0.315, P < 0.01). The 1-year FMD was significantly increased compared to the baseline FMD [(9.31 ± 5.62) % vs (7.31 ± 5.26) %, P < 0.001]. Independent predictors of FMD improvement included elevated EPC counts (OR = 1.104, 95% CI: 1.047-1.165, P < 0.001) and decreased levels of serum creatinine (OR = 0.915, 95% CI: 0.843-0.993, P = 0.034). CONCLUSIONS: Family history of premature cardiovascular diseases, hypertension, elevated systolic pressure, and HbA1c > 6.5% are independent risk factors for endothelial dysfunction in non-obstructive atherosclerotic patients. Elevated peripheral blood EPC counts and decreased levels of serum creatinine are independent predictors of endothelial function improvement.

Exosomes secreted from osteocalcin-overexpressing endothelial progenitor cells promote endothelial cell angiogenesis.

Exosome secretion is an important paracrine way of endothelial progenitor cells (EPCs) to modulate resident endothelial cells. The osteocalcin (OCN)-expressing EPCs have been found to be increased in cardiovascular disease patients and are considered to be involved in the process of coronary atherosclerosis. Since OCN has been proven to prevent endothelial dysfunction, this study aimed to evaluate the effect of exosomes derived from OCN-overexpressed EPCs on endothelial cells. Exosomes derived from EPCs (Exos) and OCN-overexpressed EPCs (OCN-Exos) were isolated and incubated with rat aorta endothelial cells (RAOECs) with or without the inhibition of OCN receptor G protein-coupled receptor family C group 6 member A (GPRC6A). The effects of exosomes on the proliferation activity of endothelial cells were evaluated by CCK-8 assay, and the migration of endothelial cells was detected by wound healing assay. A tube formation assay was used to test the influence of exosomes on the angiogenesis performance of endothelial cells. Here, we presented that OCN was packed into Exos and was able to be transferred to the RAOECs via exosome incorporation, which was increased in OCN-Exos groups. Compared with Exos, OCN-Exos had better efficiency in promoting RAOEC proliferation and migration and tube formation. The promoting effects were impeded after the inhibition of GPRC6A expression in RAOECs. These data suggest that exosomes from OCN-overexpressed EPCs have a beneficial regulating effect on endothelial cells, which involved enhanced OCN-GPRC6A signaling.

Effect of cytochrome P450 2C19 (CYP2C19) gene polymorphism and clopidogrel reactivity on long term prognosis of patients with coronary heart disease after PCI.

Objective: To investigate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity and its association with long-term clinical outcome in patients with coronary heart disease (CHD) undergoing percutaneous coronary intervention (PCI). Methods: In total, 675 patients were enrolled. Based on the platelet inhibition rate, patients were categorized into two groups: clopidogrel low responsiveness (CLR) and normal clopidogrel responsiveness (NCR). The CLR group was divided into ticagrelor and clopidogrel group based on the antiplatelet drugs used in the follow-up treatment. Patients were classified into three groups (normal metabolizer, intermediate metabolizer, and poor metabolizer) based on the CYP2C19 genotype. We aimed to evaluate the impact of CYP2C19 gene polymorphism on clopidogrel reactivity. The cumulative rates of 12-month all-cause deaths, major adverse cardiovascular events (MACCEs), and bleeding events were calculated. Results: CLR was observed in 44.4% of the overall population. Significant differences were observed in the platelet inhibition rate of clopidogrel among the three metabolic genotypes (P < 0.05). At the 12-month follow-up, 13 patients (1.9%) died and 96 patients (14.2%) experienced MACCEs. Patients with CLR (9.6% vs. 11.7% vs. 22.1%, P < 0.05) or poor metabolizer (10.7% vs. 16.4% vs. 22.6%, P = 0.026) experienced a higher rate of MACCEs. A MACCEs risk score between zero and two was calculated. The highest incidence of MACCEs significantly increased with the 2-positive results, and the area under the curve (AUC) was 0.712 (95% CI: 0.650-0.774, P < 0.05). There was no significant difference between the group with a score of one and the occurrence of MACCEs (P > 0.05). Conclusions: Low response to clopidogrel in CHD patients is correlated with CYP2C19 gene polymorphism. CYP2C19 genotyping combined with platelet reactivity is an independent predictor of 12-months MACCEs in patients with clopidogrel treatment after PCI, which is better than either test alone.

[Impact of prior cerebral infarction on in-hospital mortality in patients with acute myocardial infarction].

OBJECTIVE: To investigate the impact of prior cerebral infarction (PCI) on in-hospital mortality in patients with Acute Myocardial Infarction (AMI). METHODS: A retrospective analysis of documents of a total of 3572 consecutive patients with AMI admitted to Xuanwu Hospital of Capital Medical University from 2002 Jan. 1 to 2009 Dec. 31 were performed. RESULTS: There were 564 patients (15.8%) with PCI. Compared with the group of without PCI, the group with PCI were substantially older [(69.4 ± 9.9) vs (64.2 ± 12.9) years, P = 0.000], and had a higher prevalence of hypertensive disease, diabetes mellitus, prior myocardial infarction (MI) and non-ST-segment elevation myocardial infarction (NSTEMI) (respectively, 71.0% vs 57.3%; 41.0% vs 25.7%, 12.9% vs 9.5%; 14.9% vs 10.7%, P < 0.01), and a higher in-hospital mortality (16.5% vs 10.0%, P = 0.000). Univariate analysis demonstrated that in-hospital mortality associated with age, gender, extensive anterior MI, anterior MI, diabetes mellitus, prior cerebral infarction, prior myocardial infarction, coronary angiography and percutaneous coronary intervention. Logistic regression analysis found that risk factors were age, extensive anterior MI, anterior MI, diabetes mellitus and prior cerebral infarction, and protective factors were coronary angiography and percutaneous coronary intervention. PCI was independently associated with in-hospital mortality, OR 1.368, 95%CI 1.047 - 1.787, P = 0.022. CONCLUSION: In patients with acute myocardial infarction, the presence of PCI increases the risk of worse in-hospital outcome.

[The effects of mild hypothermia on cardiac function and myocardial structure in a rabbits model of ventricular fibrillation after restoration of spontaneous circulation].

OBJECTIVE: To examine the impact of mild hypothermia on cardiac function, myocardial tissue integrity, and 48 hours mortality in a rabbits model of ventricular fibrillation after restoration of spontaneous circulation (ROSC). METHODS: The rabbits were randomly divided into four groups: normothermic post ROSC (NTPR, n = 10), mild hypothermia post ROSC (HTPR, n = 10), normothermic control (NTC, n = 8) and mild hypothermia control (HTC, n = 8). Ventricular fibrillation was induced by trans-epicardium electric-shook with alternating current in all the animals and ROSC was achieved through administration of adrenaline (i.v.) and artificial ventilation in group NTPR and HTPR. The body temperature of the animals was kept either at (39.0 ± 0.5) centigrade (NTPR and NTC) or (33.5 ± 0.5) centigrade (HTPR and HTC) for 4 hours after surgery for hemodynamic index data collection 0.5, 1, 2, 3 and 4 hours after surgery, 48 hours later, the mortality in the animals was recorded, and myocardial tissue samples were collected from survived animals for morphological examination by light and electric microscopy and analysis of apoptosis by terminal-deoxynucleotidyl transferase mediated nick end labeling (TUNEL) staining. The content of ATP, ADP and AMP in the tissue samples was measured by high performance liquid chromatography (HPLC) for the calculation of energy charges (EC). RESULTS: (1)Hemodynamic indexes: as compared to the NTC group, HTC group exhibited significantly lower levels of heart rate (HR) and -dp/dt max in all the time points. No significant difference between the two groups in the levels of +dp/dt max and mean artery pressure (MAP) was found in all the time points but 0.5 hour. There was no significant difference in the levels of left ventricular end-diastolic pressure (LVEDP), left ventricular end-systolic pressure (LVESP), and femoral artery blood pressure between the two groups.(2) In comparison with NTPR group, HTPR group exhibited significantly (all P < 0.05) lower levels of HR (bpm) and -dp/dt max in all time points (ROSC 0.5, 1, 2, 3, 4 hours: HR 216.5 ± 33.3 vs. 292.9 ± 38.4, 218.2 ± 28.0 vs. 294.3 ± 37.0, 227.5 ± 25.4 vs. 291.4 ± 25.3, 232.4 ± 27.4 vs. 278.1 ± 30.8, 230.6 ± 22.0 vs. 285.1 ± 38.2; -dp/dt max 1847.1 ± 241.2 vs. 2383.3 ± 470.9, 1860.7 ± 167.8 vs. 2154.6 ± 319.5, 1822.3 ± 389.7 vs. 2239.7 ± 379.0, 1950.6 ± 412.9 vs. 2229.6 ± 392.4, 1875.7 ± 555.6 vs. 2396.7 ± 420.1). There was no significant difference between the two groups in the levels of LVEDP, +dp/dt max, LVESP, and femoral artery blood pressure. (3)Optical and electron microscopy revealed myocardium injury in samples from animals underwent ROSC. However, in comparison with the NTPR group, samples from HTPR group exhibited less damage to the myocardium structure. (4) Apoptosis index (AI) of myocardium was significantly (P < 0.05) higher in NTPR group (42.02%) than in HTPR group (26.39%). (5) Tests of myocardial energy: ATP level (µmol/g) in HTPR was significantly (P < 0.05) higher than NTPR (0.97 ± 0.26 vs. 0.65 ± 0.16). EC in NTPR was significant lower than it in two control groups [(0.33 ± 0.13)% vs. (0.52 ± 0.12)%, (0.55 ± 0.06)%, both P < 0.05], whereas no such difference was found between HTPR [(0.41 ± 0.12)%] and two control groups. (6) 48 hours survival rate in HTPR group was significantly higher (P = 0.043) as compared to NTPR group (100% vs. 60%). CONCLUSIONS: Myocardial dysfunction and myocardium tissue injury both develop in post-resuscitation rabbits with ventricular fibrillation. In these animals, reducing body temperature to the level of mild hypothermia after ROSC may improve the 48 hours survival rate, probably via mechanisms that suppress myocardial cell apoptosis. In our study, such intervention produced no obvious negative impact neither on the cardiac function nor hemodynamics.

The relation between serum phosphorus levels and long-term mortality in Chinese patients with ST-segment elevation myocardial infarction.

BACKGROUND: Elevated serum phosphorus levels may be associated with adverse outcomes in cardiovascular disease. This study aimed to investigate the relation between serum phosphorus levels and risk of all-cause mortality in Chinese patients with ST-segment elevation myocardial infarction (STEMI) who had preserved renal function at baseline. METHODS: We enrolled patients with STEMI who had preserved renal function at baseline in Xuanwu Hospital from January 2011 to December 2016. Those patients were divided into four groups based on serum phosphorus levels. All-cause mortality rates were compared between groups. Mean duration of follow up was 54.6 months. We used Cox proportional-hazards models to examine the relation between serum phosphorus levels and all-cause mortality after adjustment for potential confounders. RESULTS: 1989 patients were involved and 211 patients (10.6%) died during follow-up. Based on serum phosphorus levels, patients were categorized into the following groups: < 2.50 mg/dL (n = 89), 2.51-3.50 mg/dL (n = 1066), 3.51-4.50 mg/dL (n = 672) and > 4.50 mg/dL (n = 162), respectively. The lowest mortality occurred in patients with serum phosphorus levels between 2.51-3.50 mg/dL, with a multivariable-adjusted hazard ratio of 1.19 (95% CI: 0.64-1.54), 1.37 (95% CI: 1.22-1.74), and 1.46 (95% CI: 1.35-1.83) in patients with serum phosphorus levels of < 2.50 mg/dL, 3.51-4.50 mg/dL and > 4.50 mg/dL, respectively. CONCLUSIONS: Elevated serum phosphorus levels were associated with all-cause mortality in Chinese patients with STEMI who had preserved renal function at baseline.

Clinical implications of elevated serum interleukin-6, soluble CD40 ligand, metalloproteinase-9, and tissue inhibitor of metalloproteinase-1 in patients with acute ST-segment elevation myocardial infarction.

BACKGROUND: Atherosclerosis is widely accepted as a chronic inflammatory disease. Research paid much attention to sensitive specific serum biomarkers for vulnerable plaques. The markers not only serve as diagnostic tools for the identification of patients with acute coronary syndrome (ACS), but also help us to identify high-risk patients. However, the existing data are limited and have been conflicting. HYPOTHESIS: Circulating interleukin-6 (IL-6), soluble CD40 ligand (sCD40L), metalloproteinase-9 (MMP-9), and tissue inhibitor of metalloproteinase-1 (TIMP-1) might correlate with the onset and the cardiac mortality of patients with ST-segment elevation myocardial infarction (STEMI). METHODS: Serum levels of IL-6, sCD40L, MMP-9, and TIMP-1 were measured by sandwich enzyme-linked immunosorbent assay (ELISA) in 263 patients with STEMI and 262 age- and gender-matched control subjects without coronary artery disease (CAD). The patients with STEMI were then followed prospectively for 24 mo for the occurrence of cardiac mortality. RESULTS: Compared with the control subjects, patients with STEMI exhibited higher levels of IL-6 (p<0.001), sCD40L (p<0.001), MMP-9 (p<0.001), TIMP-1 (p=0.045), and MMP-9/TIMP-1 ratio (p=0.007). Significant and positive correlations between MMP-9 and TIMP-1 (r=0.610, p

Interleukin-6, but not soluble adhesion molecules, predicts a subsequent mortality from cardiovascular disease in patients with acute ST-segment elevation myocardial infarction.

Inflammatory responses are an important element in the atherosclerotic process. Therefore, inflammatory markers can potentially serve as predictors of cardiovascular risk. However, the existing data are limited and controversial. We conducted a prospective cohort study with 263 patients with first acute ST-segment elevation myocardial infarction (STEMI) who were admitted to our Hospital within 6 h after the symptoms onset. Clinical data were recorded and serum admission levels of interleukin-6 (IL-6), soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and soluble P-selectin (sP-selectin) were determined. The patients were then followed up for 3 years to document cardiovascular mortality. During the follow-up, 34 patients died from cardiovascular causes. The admission levels of IL-6 were significantly higher in these patients, whereas sICAM-1, sVCAM-1, and sP-selectin were comparable between these and the survived patients. The Kaplan-Meier plots revealed a significant increase in cardiovascular mortality with increasing levels of IL-6 (P = 0.0002, χ(2) test). The logistic regression analysis indicated that IL-6 was an independent predictor for cardiovascular mortality. To conclude, our findings indicate that elevated admission levels of IL-6, but not soluble adhesion molecules, provide valuable information for risk assessment of long-term cardiovascular mortality in patients with STEMI.

[Denitrification using polylactic acid as solid carbon source].

Polylactic acid (PLA) was used as solid carbon source and biofilm support simultaneously, to investigate the applicability of PLA in the denitrification process. The effect of temperature on denitrification performance was also studied. The IR analysis and SEM observation were performed to investigate the PLA surface structure and biofim morphology. The results showed that when the initial concentration of nitrate nitrogen was 50 mg/L and the temperature was 30 degrees C, the average denitrification rate was 2.6 x 10(-1) mg/(g x h) and nitrate could be completely removed within 13h. Temperature had a significant influence on the denitrification rate. The IR analysis and SEM observation of PLA surface structure confirmed the feasibility of PLA as solid carbon source. The SEM observation of biofim showed that the biofilm was thin and mainly consisted of cocci.

[Denitrification using radiation-pretreated wheat straw as solid carbon source].

Wheat straw after radiation pretreatment was used as solid carbon source and biofilm support for denitrifying microorganisms. Denitrification performance of radiation-pretreated wheat straw was compared to that of wheat straw without radiation pretreatment. The results showed that the denitrification rate of radiation-pretreated wheat straw was about 20% higher than that of wheat straw without radiation pretreatment. When the initial nitrate concentration was 65.3 mg/L, the denitrification rate using wheat straw after 300 kGy radiation with gamma-ray could reach 0.087 mg/(g x h) and the nitrate removal efficiency was above 90%. Parts of these results were confirmed by the IR analysis and SEM observation of wheat straw surface structure.