Role of Jagged1-Hey1 Signal in Angiotensin II-induced Impairment of Myocardial Angiogenesis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Angiotensin II (Ang II) is a major contributor to the development of heart failure. However, the molecular and cellular mechanisms that underlie this process remain elusive. Inadequate angiogenesis in the myocardium leads to a transition from cardiac hypertrophy to dysfunction, and our previous study showed that Ang II significantly impaired the angiogenesis response. The current study was designed to examine the role of Jagged1-Notch signaling in the effect of Ang II during impaired angiogenesis and cardiac hypertrophy.</p><p><b>METHODS</b>Ang II was subcutaneously infused into 8-week-old male C57BL/6 mice at a dose of 200 ng·kg-1·min-1 for 2 weeks using Alzet micro-osmotic pumps. N-[N-(3, 5-difluorophenacetyl)-L-alanyl]-S-phenylglycine tert-butyl ester (DAPT), a γ-secretase inhibitor, was injected subcutaneously during Ang II infusion at a dose of 10.0 mg·kg-1·d-1. Forty mice were divided into four groups (n = 10 per group): control group; Ang II group, treated with Ang II; DAPT group, treated with DAPT; and Ang II + DAPT group, treated with both Ang II and DAPT. At the end of experiments, myocardial (left ventricle [LV]) tissue from each experimental group was evaluated using immunohistochemistry, Western blotting, and real-time polymerase chain reaction. Data were analyzed using one-way analysis of variance test followed by the least significant difference method or independent samples t-test.</p><p><b>RESULTS</b>Ang II treatment significantly induced cardiac hypertrophy and impaired the angiogenesis response compared to controls, as shown by hematoxylin and eosin (HE) staining and immunohistochemistry for CD31, a vascular marker (P < 0.05 for both). Meanwhile, Jagged1 protein was significantly increased, but gene expression for both Jag1 and Hey1 was decreased in the LV following Ang II treatment, compared to that in controls (relative ratio for Jag1 gene: 0.45 ± 0.13 vs. 0.84 ± 0.15; relative ratio for Hey1 gene: 0.51 ± 0.08 vs. 0.91 ± 0.09; P < 0.05). All these cellular and molecular effects induced by Ang II in the hearts of mice were reduced by DAPT treatment. Interestingly, Ang II stimulated Hey1, a known Notch target, but did not affect the expression of Hey2, another Notch target gene.</p><p><b>CONCLUSIONS</b>A Jagged1-Hey1 signal might mediate the impairment of angiogenesis induced by Ang II during cardiac hypertrophy.</p>

Clinical analysis of 105 cases of ventilator-associated pneumonia after heart surgery / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the related factors and pathogens of ventilator-associated pneumonia (VAP) after heart surgery.</p><p><b>METHODS</b>VAP was diagnosed in 105 patients out of 1688 cases (6.2%) who underwent heart surgery in our department between January 2004 and January 2011. Clinical data, pathogens and treatments were analyzed.</p><p><b>RESULTS</b>Incidence of VAP was 6.2% (105/1688), and 53.0% (105/198) in patients who required more than 48 hours of mechanical ventilation. One hundred and ninety-eight pathogen strains were isolated by bacterial culture, in which Gram negative bacteria accounted for 69.2% (137/198), Gram positive bacteria 27.8% (55/198), and fungi for 3.0% (6/198). Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus were the main pathogens of VAP. The independent risk factors for VAP were: age > 70 years, emergent surgery, perioperative transfusions, reintubation and days of mechanical ventilation (all P < 0.01). Median length of stay in the ICU for patients who developed VAP or not was (24.7 ± 4.5) days versus (3.2 ± 1.5) days, respectively (P < 0.05) and in-hospital mortality was 25.7% (27/105) versus 2.9% (46/1583) respectively (P < 0.05).</p><p><b>CONCLUSIONS</b>Patients undergoing heart surgery have a high frequency of developing VAP, especially in patients that require more than 48 hours of mechanical ventilation. VAP is associated with high in-hospital mortality. Age > 70 years, emergent surgery, perioperative transfusions, reintubation and prolonged mechanical ventilation use are independent risk factors for VAP in patients following cardiac surgery. Pseudomonas aeruginosa, Klebsiella pneumoniae, Acinetobacter baumannii, Escherichia coli, and Staphylococcus aureus are the main pathogens of VAP.</p>