Bax inhibitor 1 inhibits vascular calcification in mice by activating optic atrophy 1 expression / 南方医科大学学报

OBJECTIVE@#To investigate the effects of Bax inhibitor 1 (BI- 1) and optic atrophy protein 1 (OPA1) on vascular calcification (VC).@*METHODS@#Mouse models of VC were established in ApoE-deficient (ApoE-/-) diabetic mice by high-fat diet feeding for 12 weeks followed by intraperitoneal injections with Nε-carboxymethyl-lysine for 16 weeks. ApoE-/- mice (control group), ApoE-/- diabetic mice (VC group), ApoE-/- diabetic mice with BI-1 overexpression (VC + BI-1TG group), and ApoE-/- diabetic mice with BI-1 overexpression and OPA1 knockout (VC+BI-1TG+OPA1-/- group) were obtained for examination of the degree of aortic calcification using von Kossa staining. The changes in calcium content in the aorta were analyzed using ELISA. The expressions of Runt-related transcription factor 2 (RUNX2) and bone morphogenetic protein 2 (BMP-2) were detected using immunohistochemistry, and the expression of cleaved caspase-3 was determined using Western blotting. Cultured mouse aortic smooth muscle cells were treated with 10 mmol/L β-glycerophosphate for 14 days to induce calcification, and the changes in BI-1 and OPA1 protein expressions were examined using Western blotting and cell apoptosis was detected using TUNEL staining.@*RESULTS@#ApoE-/- mice with VC showed significantly decreased expressions of BI-1 and OPA1 proteins in the aorta (P=0.0044) with obviously increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P= 0.0041). Overexpression of BI-1 significantly promoted OPA1 protein expression and reduced calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 (P=0.0006). OPA1 knockdown significantly increased calcium deposition and expressions of RUNX2, BMP-2 and cleaved caspase-3 in the aorta (P=0.0007).@*CONCLUSION@#BI-1 inhibits VC possibly by promoting the expression of OPA1, reducing calcium deposition and inhibiting osteogenic differentiation and apoptosis of the vascular smooth muscle cells.

Sphingosine-1-phosphate receptors respond differently to early myocardial ischemia and ischemia-reperfusion in vivo / 生理学报

Sphingosine-1-phosphate (S1P) has been demonstrated to be a mediator and marker of heart diseases. We hypothesized that the expression of S1P receptors is involved in the S1P-mediated cardioprotection in vivo and may serve as a biomarker of ischemic heart disease. In vivo models of myocardial ischemia (MI) and ischemia-reperfusion (IR) were established by ligation of the left anterior descending artery (LAD) of rat heart, the mRNA expressions of S1PR1-3 were detected using real time PCR at different time intervals after ischemia (LAD for 15 min, 30 min, and 1 h) and IR. The results showed that mRNA expression of S1PR3, but not S1PR1 and S1PR2, increased greatly after IR. No statistical difference was found in any of the three S1P receptors after MI within 1 h. Regarding the studies of lipid concentration changes in myocardiopathy, we conclude that S1P receptors are not early response biomarkers for MI. There are different mechanisms when S1P plays a protection role in heart during MI and IR. The cooperation of lipid content and S1P receptor expression appears to form a regulation network during MI and IR.

Prognostic value of high-sensitivity cardiac troponin T in patients with en-domyocardial-biopsy proven cardiac amyloidosis / 老年心脏病学杂志（英文版）

Objective To investigate prognostic predictors of long-term survival of patients with cardiac amyloidosis (CA), and to determine predictive value of high-sensitivity cardiac troponin T (hs-cTnT) in CA patients. Methods We recruited 102 consecutive CA cases and followed these patients for 5 years. We described their clinical characteristics at presentation and used a new, high-sensitivity assay to determine the concentration of cTnT in plasma samples from these patients. Results The patients with poor prognosis showed older age (56 ±12 years vs. 50 ±15 years, P=0.022), higher incidences of heart failure (36.92%vs. 16.22%, P=0.041), pericardial effusion (60.00%vs. 35.14%, P=0.023), greater thickness of interventricular septum (IVS) (15 ±4 mm vs. 13 ±4 mm, P=0.034), higher level of hs-cTnT (0.186 ±0.249 ng/mL vs. 0.044 ±0.055 ng/mL, P=0.001) and higher NT-proBNP (N-terminal pro-B-type natriuretic pep-tide) levels (11,742 ± 10,464 pg/mL vs. 6,031 ± 7,458 pg/mL, P=0.006). At multivariate Cox regression analysis, heart failure (HR:1.78, 95%CI:1.09-2.92, P=0.021), greater wall thickness of IVS (HR:1.44, 95%CI:1.04-3.01, P=0.0375) and higher hs-cTnT level (HR:6.16, 95%CI:2.20-17.24, P=0.001) at enrollment emerged as independent predictors of all-cause mortality. Conclusions We showed that hs-cTnT is associated with a very ominous prognosis, and it is also the strongest predictor of all-cause mortality in multivariate analysis. Examination of hs-cTnT concentrations provides valuable prognostic information concerning long-term outcomes.

The prospective register study of domestic tirofiban for clinical application in acute coronary syndrome / 中华内科杂志

Objective To evaluate the current clinical application of domestic tirofiban in patients with acute coronary syndrome (ACS) and to explore its safety profile focused on the common causes and correlation factors for the hemorrhagic events.Methods The patients diagnosed as ST-elevation myocardial infarction (STEMI) and medium to high risk non-ST-elevation myocardial infarction (NSTEMI)/ unstable angina(UA) in 15 hospitals from September 2009 to December 2011 and given domestic tirofiban,were enrolled in this study.The following data were carefully collected:demographic data,comorbidities,concomitant medications,laboratory data,interventional treatment,application of tirofiban,hemorrhagic events and major adverse cardiac events(MACE) in hospital and at day 30 after discharge.Results (1) A total of 927 patients were enrolled in the study.The domestic tirofiban was given to 241 subjects (26.0％) before the intervention,567 subjects (61.2％) during the intervention and 89 subjects (9.6％) after the intervention.The standardized application was performed in 737 subjects (79.5％) with the loading dose of 10 μg/kg and the maintenance dose of 0.15 μg · kg-1 · min-1 In all the subjects,the average maintenance time was (30.4 ± 14.2) hours with the average dose of (339.3 ± 182.9)ml.(2)During hospitalization,major bleeding happened in 4 cases(0.4％) and major adverse cardiac events (MACE) in 37 cases (4.0％).(3)At day 30 after discharge,1 cases (0.1％)was reported with major bleeding and 9 cases (1.0％) with MACE.(3)The least MACE was showed in the preoperative tirofiban group (2.5％) and followed by the intraoperative group (4.1％) and the postopcrative group (9.0％).Compared with the non-standardized application group,MACE was significantly decreased in the standardized application group (2.44％ vs 10.00％,P ＜ 0.05).Conclusions The standardized application of the domestic tirofiban could decrease the incidence of MACE.Taken into account the combination therapy of clopidogrel and aspirin in the vast majority of patients,the domestic tirofiban exhibits a good safety profile with a relatively lower incidence of bleeding than the similar clinical studies.

An analysis of factors affecting the prognosis of patients with cardiac amyloidosis / 中华内科杂志

Objective To analyze the clinical characteristics,diagnosis,treatment and outcome of patients with cardiac amyloidosis (CA).Methods Clinical data from 18 patients diagnosed as CA by endomyocardial biopsy (EMB) from 1995 to 2005 were retrospectively analyzed.Results Among the 18 patients with CA,all patients had reduced diastolic dysfunction; 12 had mitral valve early diastolic blood flow peak velocity/late diastolic blood flow peak velocity (E/A) ＞ 2.0 and ventricular diastolic early filling deceleration time (DT) ＜ 150 ms; 12 had left ventricular ejection fraction (LVEF) ＜50％ ; and 13 had New York Heart Association (NYHA) classification Ⅲ or Ⅳ.The 1-year,3-year and 5-year survival rates of 18 patients with CA were 67％,44％ and 17％,respectively.Kaplan-Meier analysis showed,NYHA functional class ＞ Ⅱ,E/A ＞ 2.0 and DT ＜ 150 ms were associated with increased mortality (log-rank statistic P =0.026 and 0.001,respectively).CA patients with chemotherapy before heart failure were associated with decreased mortality and extend survival.Conclusions The mortality rate goes up and survival rate gradually descends as prolonged onset time.NYHA functional class ＞ Ⅱ and E/A ＞ 2.0 (DT ＜150 ms) are associated with mortality.

Clinical manifestations of patients with systemic lupus erythematosus and coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics of patients with systemic lupus erythematosus (SLE) and coronary artery disease (CAD).</p><p><b>METHODS</b>Clinical data of 3911 SLE patients were retrospectively analyzed and CAD was diagnosed by coronary angiography in 26 (0.7%) SLE patients (10 stable angina pectoris, 5 unstable angina pectoris, 8 STEMI and 3 non-STEMI). The tradition risk factors, first onset of cardiac events, blood biochemistry index, treatment and activity of SLE, coronary angiographic features were compared with 552 CAD patients without SLE.</p><p><b>RESULTS</b>Compared with CAD patients without SLE, CAD patients with SLE were younger [(50.4 ± 15.2) years vs. (60.6 ± 11.6) years, P < 0.01], the mean number per patient of Framingham tradition risk factors was less (1.11 ± 1.18 vs. 2.50 ± 1.28, P < 0.05). CAD patients with SLE were prone to premature coronary artery disease [76.9% (20/26)], and ACS was the most common manifestation in SLE patients with premature coronary artery disease [65.0% (13/20)], the duration of steroid use was significantly longer [24.00 (3.75, 57.00) months vs. 1.00 (0.00, 2.00) months, P < 0.05] and 24 hours total urine protein [(1.93 ± 1.97) g vs. (0.76 ± 0.75) g, P < 0.05] was significantly higher in the ACS patients with SLE than non-ACS patients with SLE. Coronary stenosis was evidenced in most of the SLE patients with CAD [76.9% (20/26)] and incidence of coronary thrombotic occlusion was significantly higher in SLE patients with CAD than CAD patients without SLE [30.8% (8/26) vs. 11.8% (65/552), P < 0.05].</p><p><b>CONCLUSION</b>The incidence of CAD in SLE patients is low and the major form of CAD in SLE patients is premature coronary artery disease and mostly induced by coronary thrombotic occlusion.</p>

Clinical manifestations of 43 patients with acute myocardial infarction complicated by free wall rupture / 中华心血管病杂志

<p><b>OBJECTIVE</b>To analyze the clinical characteristics of patients with acute myocardial infarction (AMI) complicated by free wall rupture (FWR) and to define the independent risk factors for FWR.</p><p><b>METHODS</b>Clinical and angiographic data of 6192 AMI patients admitted to our department between January 1995 and January 2010 were retrospectively reviewed, FWR was confirmed in 43 patients by post-mortem examination. Multivariate logistic regression analysis was performed to identify risk factors for FWR.</p><p><b>RESULTS</b>Rupture occurred at a median of 3.58 days after symptom onset. Risk factors associated with FWR were older age, female gender, delayed hospital admission, hypertension at admission and increased serum creatine level. Although patients with FWR had more single-vessel disease, their in-hospital mortality was very high (97.7%). Undue physical efforts were documented in 41.9% patients with FWR.</p><p><b>CONCLUSION</b>Old age, female gender and prolonged time from the onset of symptoms to hospital, hypertension and high level of serum creatine at admission are independent factors of FWR.</p>

N-terminal pro-brain natriuretic peptide but not high-sensitivity C-reactive protein is related to severity of coronary artery stenosis in patients with acute coronary syndrome / 老年心脏病学杂志（英文版）

Objective Biochemical indicators such as N-terminal pro-brain type natriuretic peptide(NT pro-BNP)and high-sensitivity Creactive protein(hsCRP)predict mortality in acute coronary syndrome(ACS).However,little is known about the relationship of these factors with severity of coronary artery stenosis in patients with.Methods Three hundred and thirty-one subjects including 246 unstable angina pectoris patients and 85 myocardial infarction patients were recruited and classified into two groups:single-vessel disease group(1-vessel disease,n=93)and multiple-vessel disease group(≥2-vessels disease,n=238)according to selective coronary angiography.Plasma levels of NT pro-BNP and hsCRP were measured and severity of coronary stenosis was determined by Gensini score.Results NT pro-BNP but not hsCRP level was higher in patients with myocardial infarction than in patients with unstable angina pectoris.The patients with multiple-vessel disease had significantly higher NT pro-BNP level but not hsCRP compared with those with single-vessel disease.NT pro-BNP levels increased significantly as left ventricle(LV)function decreased,and only NT proBNP but not hsCRP level was related to Gensini score of severity of coronary stenosis in ACS.Conclusion NT proBNP but not hsCRP level is related to severity of coronary artery stenosis in patients in ACS.