Macrophages enhance lipopolysaccharide induced apoptosis via Ang1 and NF-κB pathways in human umbilical vein endothelial cells.

Lipopolysaccharide (LPS) could induce apoptosis and dysfunction of endothelial cells. We aimed to reveal the effects of macrophages on cell proliferation and apoptosis in LPS induced human umbilical vein endothelial cells (HUVECs). THP-1 derived macrophages and HUVECs were co-cultured in the presence of LPS. Cell viability was measured by Cell Counting Kit-8 and apoptosis was analyzed by flow cytometry. Expression of Ang1, the NF-κB component p65 was evaluated by western blot and quantitative PCR. Small interfering RNAs (siRNAs) were used to knockdown the expression of proinflammatory cytokines and p65 in HUVECs. Plasmid transfection-mediated overexpression of Ang1 was employed to see its effects on cell proliferation and apoptosis in HUVECs. Macrophages enhanced LPS-induced proliferation impairments and apoptosis in HUVECs, which could be attenuated by siRNA-mediated knockdown of cytokines TNF-α, IL-1ß, IL-6 and IL-12p70 in macrophages. The dysfunction of HUVECs was tightly associated with reduced Ang1 expression and increased phosphorylated p65 (p-65). Overexpression of Ang1 in HUVECs significantly decreased p-p65, suggesting negatively regulation of p-p65 by Ang1. Overexpression of Ang1, adding recombinant Ang1 or silencing of p65 substantially attenuated the dysfunction of HUVECs in terms of cell proliferation and apoptosis. In conclusions, THP-1-derived macrophages enhance LPS induced dysfunction of HUVECs via Ang1 and NF-κB pathways, suggesting new therapeutic targets for sepsis.

Value of plasma brain natriuretic peptide levels for predicting postoperative atrial fibrillation: a systemic review and meta-analysis.

BACKGROUND: Blood natriuretic peptide (NP) levels have been reported to be useful for predicting postoperative atrial fibrillation (AF). We aimed to quantitatively synthesize the current evidence of the accuracy of using NP levels in predicting postoperative AF. METHODS AND RESULTS: Medline, Embase, and reference lists were searched. Studies were included if either brain natriuretic peptide (BNP) or N-terminal pro-b type natriuretic peptide (NT-proBNP) had been evaluated perioperatively to predict postoperative AF. Data were analyzed to obtain summary accuracy estimates. Data from 1,844 patients in 10 studies were analyzed. Summary estimates for the sensitivity and specificity of using NP levels for predicting postoperative AF were 75 % [95 % confidence interval (CI) 67-79 %] and 80 % (95 % CI 62-91 %), respectively. The overall diagnostic odds ratio was 3.28 (95 % CI 2.23-4.84). Subgroup analysis showed that elevated NP levels in the perioperative period were a strong independent predictor of postoperative AF. NT-proBNP appeared to have better predictive value than BNP, as did postoperative assessment over preoperative assessment. BNP had a better correlation with postoperative AF in patients undergoing thoracic surgery than in patients undergoing cardiac surgery. CONCLUSIONS: Perioperative assessment of the natriuretic peptide level in patients undergoing major cardiothoracic surgery could be a valuable diagnostic aid for identifying patients at high risk of developing postoperative AF, and for providing critical clinical information to guide prophylactic antiarrhythmic therapy in the perioperative period.

[Microcirculation characters in the elderly septic patients].

OBJECTIVE: To explore the changes of sublingual microcirculation in elderly patients with severe sepsis/septic shock. METHODS: Twenty-three patients with sepsis, 10 patients without sepsis and 10 healthy elderly patients were enrolled. Sublingual microcirculation was evaluated by sidestream darkfield (SDF) imaging. And the 28-day mortality rates of all septic patients were recorded. RESULTS: Compared with the healthy group, all elderly patients had significant sublingual microcirculation dysfunctions. Compared with the severe septic and nonseptic patients, perfused vessel density (PDV) , proportion of perfused vessels (PPV) and microvascular flow index (MFI) of septic shocks were significantly lower. Compared with the severe septic patients, PDV, PPV and MFI instead of lactate and MAP of septic shocks were significantly lower from Day 1 to Day 3. The values of PDV, PPV, MFI and lactate but not MAP of the surviving septic patients were significantly higher than those of the deceased ones. CONCLUSIONS: The elderly patients with septic shock have severe sublingual microcirculatory alterations. And these abnormalities are more marked in septic shock patients. Nonsurvivors showed more severe alterations than survivors. Microcirculatory alterations may be measured to guide the therapy.

[An evaluation of stroke volume variation as a predictor of fluid responsiveness in mechanically ventilated elderly patients with severe sepsis].

OBJECTIVE: To evaluate stroke volume variation (SVV) as a predictor of fluid responsiveness in mechanically ventilated (MV) elderly patients with severe sepsis. METHODS: A prospective observation of 31 fluid challenges during fluid resuscitation for treatment of hemodynamic instability in 17 elderly MV patients with severe sepsis was conducted. SVV was measured by pulse indicator continuous cardiac output (PiCCO) system. Fluid responsiveness was defined as the changes in cardiac index (CI) increase after fluid loading (DeltaCI) > or =10%. The changes in hemodynamic parameters and lung water index were observed at the onset of and after fluid therapy. The correlation between DeltaCI and SVV or central venous pressure (CVP) were analyzed. RESULTS: SVV was decreased significantly after fluid loading [(6.6+/-2.1)% vs.(12.1+/-3.7)%, P<0.01], whereas CVP increased significantly [(12.5+/-3.6) mm Hg vs. (8.9+/-4.1) mm Hg, 1 mm Hg=0.133 kPa, P<0.01]. DeltaCI in response to fluid loading were positively correlated to initial values of SVV (r=0.447, P=0.012), but there was no relationship between CVP and DeltaCI (r=-0.082, P=0.674). The areas under the receiver operating characteristic curve (ROC curve) for SVV was 0.672 [95% confidence interval (95%CI) 0.463-0.885] and CVP was 0.336 (95%CI 0.133-0.539), respectively. A SVV value of 11.5% had the sensitivity of 71% and specificity of 67% for prediction of fluid responsiveness. CONCLUSION: Functional hemodynamic parameter SVV can predict fluid responsiveness in elderly MV patients with severe sepsis during fluid resuscitation, it may serve as a useful index for guiding fluid therapy in elderly patients with severe sepsis.

[A novel missense mutation, K124N, in the troponin T gene of Chinese populations with hypertrophic cardiomyopathy].

OBJECTIVE: To study the cardiac troponin T (TNNT2) gene mutation in Chinese patients with hypertrophic cardiomyopathy (HCM) and to analyze the correlation between the genotype and phenotype. METHODS: Specimens of peripheral blood were collected from 71 unrelated Chinese probands with HCM, aged 40 +/- 18. The genome DNA was extracted. Single-strand conformation polymorphism gel analysis of the polymerase chain reaction-amplified products was conducted to search for mutations in the exons 8, 9, 10, 11, and 16 of the TNNT2 gene. Relevant clinical data were collected. One hundred normal persons, aged 44 +/- 14, were used as controls. RESULTS: A missense mutation, K124N, in the exon 9 of the TNNT2 gene was identified in a 41-year-old female patient with HCM and failed to be detected in the 100 normal controls, which suggested the disease-causing mutation. The patient began to have the symptoms of chest distress and palpitation since the age of 38, presented moderate hypertrophy of the intraventricular septum, and did not have a family history of sudden cardiac death. CONCLUSION: A novel missense mutation of troponin T gene has been identified. Mutation in tail part of cardiac troponin T, essential for it's binding function, causes the disease of HCM. Correlative analysis confirms the genetic heterogeneity of the disease.