Antiplatelet Therapy, Clinical Characters and Long-term Outcomes of Patients With Angiography-documented Stent Thrombosis / 中国循环杂志

Objectives: To describe the differences between patients with angiography confirmed stent thrombosis in antiplatelet therapy and long term outcomes. Methods: We analyzed data from 1 204 patients with angiography – documented stent thrombosis between January 2008 to December 2016 in Beijing Anzhen Hospital. According to the timing of stent thrombosis post stent implantation, patients were divided into acute stent thrombosis (<24 h, n=106), subacute stent thrombosis(24 h~30 d, n=206), late stent thrombosis (>30 d~1y, n=268), and very late stent thrombosis (>1 y, n=624) groups. Death, recurrent stent thrombosis, recurrent myocardial infarction, target vessel revascularization, stroke and antiplatelet treatment during In-hospital or long-term clinical follow-up were compared among groups. Results: Prevalence of stent thrombosis was the highest in the left anterior descending artery (51.9%) in acute stent thrombosis group. Subjects with subacute stent thrombosis had a higher prevalence rate of LVEF<50% (28.2%), and subjects with very late stent thrombosis had a higher prevalence rate of diabetes (34.1%). All patients in acute stent thrombosis group received aspirin + clopidogrel, 96.5% patients in subacute stent thrombosis group and 94.5% patients in late stent thrombosis group were treated with double or triple antiplatelet therapy, while 95.2% patients in the very late stent thrombosis group were treated with double or mono antiplatelet therapy. During the follow up, mortality was 23.6%, 26.7%, 26.3% and 18.9% in acute stent thrombosis, subacute stent thrombosis, late stent thrombosis, and very late stent thrombosis groups, respectively. Conclusions: Most patients with angiography–documented stent thrombosis are treated with recommended antiplatelet therapy. Development of stent thrombosis is associated with poor outcomes.

Ultrasonic destruction of albumin microbubbles enhances gene transfection and expression in cardiac myocytes / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It has been proven that ultrasonic destruction of microbubbles can enhance gene transfection efficiency into the noncardiac cells, but there are few reports about cardiac myocytes. Moreover, the exact mechanisms are not yet clear; whether the characteristic of microbubbles can affect the gene transfection efficiency or not is still controversial. This study was designed to investigate whether the ultrasound destruction of gene-loaded microbubbles could enhance the plasmids carried reporter gene transfection in primary cultured myocardial cell, and evaluate the effects of microbubbles characteristics on the transgene expression in cardiac myocytes.</p><p><b>METHODS</b>The β-galactosidase plasmids attached to the two types of microbubbles, air-contained sonicated dextrose albumin (ASDA) and perfluoropropane-exposed sonicated dextrose albumin (PESDA) were prepared. The gene transfection into cardiac myocytes was performed in vitro by naked plasmids, ultrasound exposure, ultrasonic destruction of gene-loaded microbubbles and calcium phosphate precipitation, and then the gene expression and cell viability were analyzed.</p><p><b>RESULTS</b>The ultrasonic destruction of gene-loaded microbubbles enhanced gene expression in cardiac myocytes compared with naked plasmid transfection ((51.95 ± 2.41) U/g or (29.28 ± 3.65) U/g vs. (0.84 ± 0.21) U/g, P < 0.01), and ultrasonic destruction PESDA resulted in more significant gene expression than ASDA ((51.95 ± 2.41) U/g vs. (29.28 ± 3.65) U/g, P < 0.05). Ultrasonic destruction of microbubbles during calcium phosphate precipitation gene transfection enhanced β-galactosidase activity nearly 8-fold compared with calcium phosphate precipitation gene transfection alone ((111.35 ± 11.21) U/g protein vs. (14.13 ± 2.58) U/g protein, P < 0.01). Even 6 hours after calcium phosphate precipitation gene transfection, ultrasound-mediated microbubbles destruction resulted in more intense gene expression ((35.63 ± 7.65) U/g vs. (14.13 ± 2.58) U/g, P < 0.05).</p><p><b>CONCLUSIONS</b>Ultrasonic destruction of microbubbles might be a promising method for the delivery of non-viral DNA into cardiac myocytes, and the gene tranfection is related to the characteristics of microbubbles.</p>

Oxidized low density lipoprotein and peroxisome proliferator-activated receptor α induced endogenous fibroblast growth factor 21 upregulation is protective against apoptosis in cardiac endothelial cells / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the effect of peroxisome proliferator-activated receptor (PPAR)α agonist bezafibrate and oxidized low density lipoprotein (ox-LDL) on fibroblast growth factor 21 (FGF21) expression and apoptosis in cardiac endothelial cells.</p><p><b>METHODS</b>The mRNA level of FGF21 was determined by real time-PCR and the protein concentration of FGF21 in culture media was detected by enzyme-linked immunosorbent assay in cultured cardiac microvascular endothelial cells (CMECs) incubated with 10, 50, 100 µg/ml ox-LDL, 50, 100 or 200 µmol/L bezafibrate alone or in combination with 100 µg/ml ox-LDL. CMECs apoptosis in various treatment groups was also determined.</p><p><b>RESULTS</b>FGF21 mRNA and protein expressions were significantly upregulated in proportion to increased ox-LDL, and 200 µmol/L bezafibrate alone also significantly upregulated FGF21 expression and CMECs apoptosis was significantly reduced in 200 µmol/L bezafibrate + 100 µg/ml ox-LDL group compared to 100 µg/ml ox-LDL group (P < 0.05).</p><p><b>CONCLUSIONS</b>Our data suggest that bezafibrate and ox-LDL induced upregulation of FGF21 might mediate the protective effect against apoptosis. Endogenous FGF21 could thus play important roles in improving the endothelial function at the early stage of atherosclerosis and slowing the development of coronary heart disease.</p>

Fibroblast growth factor 21 as a possible endogenous factor inhibits apoptosis in cardiac endothelial cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Fibroblast growth factor 21 (FGF21) is a new member of FGF super family that is an important endogenous regulator for systemic glucose and lipid metabolism. This study aimed to explore whether FGF21 reduces atherosclerotic injury and prevents endothelial dysfunction as an independent protection factor.</p><p><b>METHODS</b>The present study was designed to investigate the changes of FGF21 levels induced by oxidized-low density lipoprotein (ox-LDL), and the changes of apoptosis affected by regulating FGF21 expression. The FGF21 mRNA levels of cultured cardiac microvascular endothelial cells (CMECs) were determined by real time-PCR and the protein concentration in culture media was detected by enzyme-linked immunosorbent assay. We analyzed the different expression levels of untreated controls and CMECs incubated with ox-LDL, and the changes of CMECs apoptosis initiated by the enhancement or suppression of FGF21 levels.</p><p><b>RESULTS</b>The secretion levels of FGF21 mRNA and protein were significantly upregulated in CMECs incubated with ox-LDL. Furthermore, FGF21 levels increased by 200 µmol/L bezafibrate could reduce CMECs apoptosis, and inhibit FGF21 expression by shRNA induced apoptosis (P < 0.05).</p><p><b>CONCLUSIONS</b>FGF21 may be a signal of injured target tissue, and may play physiological roles in improving the endothelial function at an early stage of atherosclerosis and in stopping the development of coronary heart disease.</p>

Using the combination of traditional risk factors and quantitative coronary angiography (QCA )in predicting the risk of individuals with subclinical artherosclerosis / 中华流行病学杂志

Objective To determine whether the combination of traditional risk factors and quantitative coronary angiography (QCA) assessment could provide accurate prognostic information on a population-based study including 1137 adults with subclinical artherosclerosis and with coronary risk factors. Methods Participants underwent coronary angiography examination before the minimal stenotic diameters, segment diameters, percent stenosis, plaque areas. Other parameters were analyzed by the computer-assisted Coronary Angiography Analysis System. The Framingham Risk Score for each participant was assessed. During the 1 year follow-up period, all kinds of endpoint cardiovascular events were screened. Endpoint events were defined as death from coronary heart disease, nonfatal myocardial infarction (MI) or unstable angina pectoris. Results During the 1 year of follow-up period, a total of 124 participants developed an endpoint event, which was significantly associated with the Framingham Risk Score, calcium of plaques and the plaque areas (all Ps＜0.05).The QCA score incorporated with the QCA parameters was related to the endpoint events. The Framingham Risk Score was combined with QCA score through logistic regression for prediction of end-point events. Data from the ROC analysis showed the accuracy of this prediction algorithm was superior to the accuracy when variables themselves were used. The event-free survival rate was inferior to the control group in participates under high risk, when being screened with this prediction algorithm (P＜0.05). Conclusion The risk of cardiovascular attack in subclinical artherosclerosis individual seemed to be associated with the Framingham Risk Score, calcium of plaques and the plaque areas. When the traditional risk factors (the Framingham Risk Score) were combined with QCA, the new method could provide more prognostic information on those adults with subclinical artherosclerosis.

Quantitative coronary angiography and intravascular ultrasound assessments on target lesion and reference vessel in patients with diabetes mellitus / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the accuracy of quantitative coronary angiography (QCA) assessment on target lesion and reference vessel in patients with diabetes mellitus with intravascular ultrasound (IVUS) measurements as golden standard.</p><p><b>METHODS</b>QCA and IVUS were performed in 52 diabetes mellitus patients [35 males, mean age (62.3 +/- 7.1) years]. Regression equation was ascertained with the IVUS derived plaque burden as dependent and QCA derived vessel stenosis as independent variable. The measurement results derived from the two modalities on proximal and distal reference vessels were compared.</p><p><b>RESULT</b>The regression equation (constant = 0.8286, P = 0.001) of plaque burden and vessel stenosis derived from two modalities were significantly correlated (r = 0.691, P < 0.001) but QCA overestimated the stenosis severity (57.9% +/- 15.5% vs. 53.5% +/- 12.9%, P < 0.01). Target vessels negative remodeling index in these patient was 0.87 +/- 0.23. QCA significantly underestimated the proximal and distal reference segments vessel diameters [(0.81 +/- 0.24) mm, (0.64 +/- 0.17) mm, all P < 0.05] as compared to IVUS results.</p><p><b>CONCLUSION</b>Due to the significant negative vessel remodeling, QCA overestimated the stenosis severity and underestimated the reference segments vessel diameters in patients with diabetes mellitus.</p>

Value of intravascular ultrasound, 64 multi-detector computed tomography and quantitative coronary angiography on lesion of coronary artery in unstable angina pectoris patient / 中华心血管病杂志

<p><b>OBJECTIVE</b>To compare the value of intravascular ultrasound (IVUS) and assess the value of quantitative coronary angiography (QCA) and 64 multi-detector computed tomography (MDCT) on unstable anginas (UAP) risk stratification.</p><p><b>METHOD</b>A total of 61 UAP patients (low risk: 17, middle risk: 33 and high risk: 11) were recruited, 71 vessels were examined by MDCT, QCA and IVUS. Plaque characteristics (soft, fibrous, calcified and mixed plaques) and plaque burden at minimum area (< or = 50%, 51% - 74% and > or = 75%) were detected, calculated and analyzed. Results derived from various detection methods were compared.</p><p><b>RESULTS</b>Plaque burden detection by QCA was comparable to IVUS results for low and middle risk UAP (r = 0.768 and r = 0.721, respectively; all P < 0.01) but not for high risk UAP (67% + or - 14% vs.75% + or - 16%, P < 0.01) due to significant positive vessel remodeling (remodeling index = 1.21 + or - 0.31). The high negative predict value of MDCT for stenosed coronary vessels (87.8% - 96.3%)was valuable for exclusion of coronary heart disease but MDCT was not able to identify fibrous cap (kappa = 0.235) and lipid core (kappa = 0.245). Extent of remodeling index, external elastic membrane area, minimum lumen area, plaque burden, plaque rupture and thrombosis increased in proportion to increasing risks of UAP patients.</p><p><b>CONCLUSIONS</b>QCA is a suitable tool for assessing UAP patients with low and middle vessel stenosis but underestimated the stenosis degree in UAP patients with high vessel stenosis. MDCT is valuable for exclusion vessel disease but not useful for identifying soft and fibrous plaque. Soft plaque with positive remodeling index and minimum lumen area < 4 mm(2) derived from IVUS could correctly identify UAP patients with high degree of vessel stenosis.</p>

The changes in the mRNA levels of calcium regulatory proteins in ischemia/reperfusion rat ventricles / 中国应用生理学杂志

<p><b>AIM</b>To investigate the changes in the expression of four kinds of calcium regulatory proteins mRNA on the isolated ischemia/ reperfusion (IR) hearts.</p><p><b>METHODS</b>The rat hearts were divided into two groups: control group and IR group which received 45 min exposure to Krebs-Henseleit solution after 15 min zero-flow global ischemia. The indexes of left ventricular function, such as LVDP, +dp/dt(max), -dp/dt(max), and an arrhythmia scoring system were compared between the two groups. The messenger ribonucleic acid (mRNA) amount of sarcoplasmic reticulum (SR) Ca2+ ATPase (SERCA), phospholamban (PLB), inositol 1,4,5-trisphosphate receptor2 (IP3R2) and ryanodine receptor2 (RyR2) was measured by reverse transcription-polymerase chain reaction (RT-PCR) and normalized to the mRNA levels of beta-actin.</p><p><b>RESULTS</b>In the IR group, LVDP, +dp/dt(max) and -dp/dt(min) of the isolated hearts were depressed and the high rate of arrhythmias occurred during reperfusion. The levels of SERCA, IP3R2, RyR2 mRNA were lower in the IR isolated hearts group than those in the control group, while there was no difference in the level of phospholamban.</p><p><b>CONCLUSION</b>These data suggest that myocardial ischemia/reperfusion can induce the depression of cardiac performance and an increased risk of arrhythmias, concomitant with the decrease in SERCA, IP3R2, RyR2 mRNA steady state levels.</p>

Enhanced reporter gene transfer and expression in cardiac myocytes mediated by ultrasonic destruction of the microbubbles / 中国应用生理学杂志

<p><b>AIM</b>To determine if the diagnostic ultrasound and self-made microbubbles could be used to increase gene transfection and expression in cardiac myocytes by means of the ultrasound-mediated microbubbles destruction.</p><p><b>METHODS</b>The perfluoropropane-exposed sonicated dextrose albumin(PESDA) microbubbles were made and mixed with indicated volume reporter gene encoding beta-galactosidase prior to gene transfection. Gene transfection into the cultured cardiac myocytes was performed by exposure to the various intense diagnostic ultrasound (1.3 MHz) in the presence of the gene-attached microbubbles. The calcium phosphate precipitation gene transfection was carried out alone or in combination with ultrasound-mediated destruction microbubbles. The cells were harvested 48 h after transfection and beta-galactosidase expression was detected by in situ staining and quantitive assay.</p><p><b>RESULTS</b>Cardiac myocytes exposed to ultrasound with PESDA induced significantly increase in gene expression (60-fold compared with naked plasmids transfection, P < 0.01). Moreover, it was found that the reporter gene expression not only related with ultrasound intension but also with the microbubbles concentration. In combination with calcium phosphate precipitation gene transfection, ultrasound-mediated destruction microbubbles resulted in more intense gene expression even 6 hours after calcium phosphate precipitation gene transfection.</p><p><b>CONCLUSION</b>The ultrasonic destruction of gene-loaded microbubble is a highly effective gene transfer method, and it not only acts on the gene entry into cells, but also on the intracellular exogenous DNA expression.</p>

Study of platelet membrane glycoprotein expression in mice with decompression sickness / 中华劳动卫生职业病杂志

<p><b>OBJECTIVE</b>To investigate the role of expression of platelet membrane glycoprotein CD31, CD61 and CD62p in the pathogenesis of decompression sickness.</p><p><b>METHODS</b>Mice were randomly divided into decompression sickness group and normal control group. The animals in decompression sickness group were exposed to 600 kPa compressed air for 60 minute, then they were rapidly decompressed to normal pressure in one minute. At 60th minute after reducing to normal pressure, the expression of CD31, CD61 and CD62p on platelet membrane in mice was measured by flow cytometry.</p><p><b>RESULTS</b>The mean fluorescence intensity of CD31, CD61 and positive percentage of CD62p on platelet membrane [(18.64 +/- 1.01), (271.06 +/- 24.25), (4.48% +/- 0.43%) respectively] in decompression sickness group were significantly increased compared with normal control group [(16.89 +/- 1.69), (234.09 +/- 15.96), (3.00% +/- 0.66%) respectively] (P < 0.05, P < 0.01).</p><p><b>CONCLUSION</b>Inadequately rapid decompression may induce up regulation of platelet membrane glycoprotein CD31, CD61 and CD62p expression in mice, which may lead to thrombosis.</p>