Impact of inflammatory reaction levels and culprit plaque characteristics on preprocedural thrombolysis in myocardial infarction flow grade in patients with ST-segment elevation myocardial infarction / 中华心血管病杂志

Objective: To determine the impact of inflammatory reaction levels and the culprit plaque characteristics on preprocedural Thrombolysis in Myocardial Infarction (TIMI) flow grade in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Methods: The is a retrospective study. A total of 1 268 STEMI patients who underwent pre-intervention optical coherence tomography (OCT) examination of culprit lesion during emergency PCI were divided into 2 groups by preprocedural TIMI flow grade (TIMI 0-1 group (n =964, 76.0%) and TIMI 2-3 group (n =304, 24.0%)). Baseline clinical data of the 2 groups were collected; blood samples were collected for the detection of inflammatory markers such as high sensitivity C-reactive protein (hsCRP), myocardial injury marker, blood lipid, etc.; echocardiography was used to determine left ventricular ejection fraction; coronary angiography and OCT were performed to define the lesion length, diameter stenosis degree of the infarct-related arteries, presence or absence of complex lesions, culprit lesion type, area stenosis degree and vulnerability of culprit plaques. Multivariable logistic regression analysis was performed to identify independent correlation factors. The receiver operating characteristic (ROC) curve of continuous independent correlation factors was analyzed, and the best cut-off value of TIMI 0-1 was respectively determined according to the maximum value of Youden index. Results: The mean age of 1 268 STEMI patients were (57.6±11.4) years old and 923 cases were males (72.8%). Compared with TIMI 2-3 group, the patients in TIMI 0-1 group were older and had higher N-terminal-pro-B-type natriuretic peptide level, lower cardiac troponin I (cTnI) level, lower left ventricular ejection fraction, and higher hsCRP level (5.16(2.06, 11.78) mg/L vs. 3.73(1.51, 10.46) mg/L). Moreover, the hsCRP level of patients in TIMI 0-1 group was higher in the plaque rupture subgroup (all P<0.05). Coronary angiography results showed that compared with TIMI 2-3 group, the proportion of right coronary artery (RCA) as the infarct-related artery was higher, the angiographical lesion length was longer, minimal lumen diameter was smaller, and diameter stenosis was larger in TIMI 0-1 group (all P<0.05). The prevalence of plaque rupture was higher (75.8% vs. 61.2%) in TIMI 0-1 group. Plaque vulnerability was significantly higher in TIMI 0-1 group than that in TIMI 2-3 group with larger mean lipid arc (241.27°±46.78° vs. 228.30°±46.32°), more thin-cap fibroatheroma (TCFA, 72.4% vs. 57.9%), more frequent appearance of macrophage accumulation (84.4% vs. 70.7%) and cholesterol crystals (39.1% vs. 25.7%). Minimal flow area was smaller [1.3(1.1-1.7)mm2 vs. 1.4(1.1-1.9)mm2, all P<0.05] and flow area stenosis was higher (78.2%±10.6% vs. 76.3%±12.3%) in TIMI 0-1 group. Multivariable analysis showed that mean lipid arc>255.55°, cholesterol crystals, angiographical lesion length>16.14 mm, and hsCRP>3.29 mg/L were the independent correlation factors of reduced preprocedural TIMI flow grade in STEMI patients. Conclusions: Plaque vulnerability and inflammation are closely related to reduced preprocedural TIMI flow grade in STEMI patients.

Application of metabolomics in coronary heart disease detection and its progress / 心血管康复医学杂志

:In recent years ,many techniques have been used for detection of coronary heart disease (CHD) ,especially the novel metabolomic technique .Metabolic disorder may probably be associated with cardiovascular diseases ,and i‐dentified new metabolic features or products may expand risk predictive model .The present article made a review on research progress of metabolic analysis and metabolomics in cardiovascular disease field in recent years .

Recombinant Human Thioredoxin-1 Protects Macrophages from Oxidized Low-Density Lipoprotein-Induced Foam Cell Formation and Cell Apoptosis

Oxidized low-density lipoprotein (ox-LDL)-induced macrophage foam cell formation and apoptosis play critical roles in the pathogenesis of atherosclerosis. Thioredoxin-1 (Trx) is an antioxidant that potently protects various cells from oxidative stress-induced cell death. However, the protective effect of Trx on ox-LDL-induced macrophage foam cell formation and apoptosis has not been studied. This study aims to investigate the effect of recombinant human Trx (rhTrx) on ox-LDL-stimulated RAW264.7 macrophages and elucidate the possible mechanisms. RhTrx significantly inhibited ox-LDL-induced cholesterol accumulation and apoptosis in RAW264.7 macrophages. RhTrx also suppressed the ox-LDL-induced overproduction of lectin-like oxidized LDL receptor (LOX-1), Bax and activated caspase-3, but it increased the expression of Bcl-2. In addition, rhTrx markedly inhibited the ox-LDL-induced production of intracellular reactive oxygen species (ROS) and phosphorylation of p38 mitogen-activated protein kinases (MAPK). Furthermore, anisomycin (a p38 MAPK activator) abolished the protective effect of rhTrx on ox-LDL-stimulated RAW264.7 cells, and SB203580 (a p38 MAPK inhibitor) exerted a similar effect as rhTrx. Collectively, these findings indicate that rhTrx suppresses ox-LDL-stimulated foam cell formation and macrophage apoptosis by inhibiting ROS generation, p38 MAPK activation and LOX-1 expression. Therefore, we propose that rhTrx has therapeutic potential in the prevention and treatment of atherosclerosis.

Research progress for antitumor drug treating coronary artery disease / 心血管康复医学杂志

The present article summarizes research progress for anti-tumor drug relating coronary artery disease, reviews domestic and foreign relevant literature about it and makes a review about its research progress. Its mechanism is multi-level and multi-site. Some anti-tumor drug are expected to be new targets of treating coronary artery disease.

Morphologic characteristics of late stent malapposition after drug-eluting stents implantation by optical coherence tomography follow-up / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Late stent malapposition was frequently observed after DES implantation, which has been associated with the occurrence of late stent thrombosis due to poor neointimal coverage. This study was designed to evaluate the frequency of late stent malapposition at least 1 year after different DESs implantation by optical coherence tomography (OCT).</p><p><b>METHODS</b>Angiographic and OCT examinations were given to 68 patients who had received total 126 various DESs implantation for at least 1 year to detect late stent malapposition. Malapposed strut distance (MSD), malapposed strut area (MSA), reference lumen area (RLA) and reference stent area (RSA) were checked with off-line OCT analysis.</p><p><b>RESULTS</b>Totally 26 Cypher Select stents, 15 Taxus Liberte stents, 51 Partner stents and 34 Firebird I stents were examined. Among 68 patients who underwent DES implantation, 7 patients (10.3%) had late malapposition. Average RSA, MSA and MSD were (7.9 +/- 2.8) mm(2),(2.0 +/- 1.6) mm(2) and (590 +/- 270) microm respectively. According to the MSA/RSA ratio, 4 patients had slight malapposition, 2 patients had moderate malapposition and 1 patient had severe malapposition.</p><p><b>CONCLUSIONS</b>Late stent malapposition is detected frequently after implantation of DES, but if this predisposes to late stent thrombosis and requires any specific therapy needs to be further elucidated.</p>

Effect of adenovirus-mediated local tissue factor pathway inhibitor gene transfer on thrombosis formation in rabbit carotid artery injuries / 中国地方病学杂志

Objective To observe the effects of tissue factor pathway inhibitor(TFPI) on thrombosis formation in rabbit carotid arteries after ballon injury. Methods Fouty rabbits with the weight 2.5-3.0 kg were respectively divided into 4 groups, Ad-TFPI, Ad-LacZ, PBS and normal control groups. The normal control group was not given any treatment and other 3 groups were given 0.2 ml Ad-TFPI, Ad-LacZ or PBS reproduced by the Dispatch catheter respectively after the PTCA balloon iniury on the right carotid arteries. Ten days after gene transfer the repeated balloon injury was performed in the 3 groups, and the first balloon injury was performed in the normal control group by the same method. The carotid blood flow was recovered immediately after the injury. Thirty minutes later all the animals were sacrificed. The injured carotid arteries and one part of contralateral normal artery were cut down, scissored along the long axis, flattened and fixed in the 2% glutaral. The platelet aggregation and thrombosis formation on the luminal surfaces was observed under electron microscope. Results The electron microscope results showed that the vascular endothelial cell structure was integrated and lined up in order in the nomal artery which had no any injury. After the balloon injury in the normal control group, the structure of the endothelial cell was disintegrated, and there was some platelet aggregation but no fibrosis formation. A large amount of platelet aggregated but no fibrosis formed in Ad-TFPI group after the repeated balloon injury. A large amount of fibrosis formed and red cells piled up in the Ad-LacZ and PBS group. The positive rate of thrombosis formation among groups had siginificant differences(χ2=14.95, P<0.01). The positive rate in Ad-TFPI group(20%) was lower than that in Ad-LacZ group(80%, χ2=7.20, P<0.01) and PBS group(70%, χ2=5.05, P<0.05), but was higher than that in the normal control group(10%, χ2=0.39, P>0.05). The positive rate in Ad-LacZ group(80%) was higher than in the normal control group(10%, χ2=9.90, P<0.01) and in the PBS group(70%, χ2=0.27, P> 0.05). The positive rate in PBS group(70%) was higher than that in the normal control group(10%, χ2=7.50, P< 0.01). Conclusions The repeated balloon injury method can cause a large amount of fibrosis formation in the rabbit carotid. TFPI gene inhibits thrombosis formation in balloon-injured rabbit carotid arteries.

Ad-TFPI gene transfer attenuates intimal proliferation in rabbit carotid arteries after balloon injury / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the in vivo gene expression of adenovirus-mediated human tissue factor pathway inhibitor (hTFPI) and its inhibition effects on intimal proliferation in rabbit carotid arteries after balloon injury.</p><p><b>METHODS</b>Rabbits underwent carotid artery balloon injuries were treated with Ad-TFPI (n = 25), Ad-LacZ (n = 25) or PBS (n = 10), respectively. Sham operated rabbits (n = 10) serve as normal controls. The expressions of human TFPI at mRNA and protein levels were detected by RT-PCR and ELISA respectively on the 3rd, 7th, 10th, 14th, 28th day after operation. Intimal proliferation was detected by angiograms and morphometric analysis.</p><p><b>RESULTS</b>TFPI mRNA and protein expressions were detected at 3 days and peaked at the 10th and 14th day after TFPI gene transfer. The expressions were still detectable on the 28th day. There was no TFPI expression in Ad-LacZ group. The carotid angiogram results indicated that the minimal lumen diameter in TFPI group was significantly larger and the lumina stenosis percentage was significantly lower in TFPI group compared those in Ad-LacZ and PBS groups (all P < 0.05). The morphometric analysis showed that the intimal area, the ratio of the intimal/media area, the lumina stenosis percentage in TFPI group were all significantly reduced compared with those in Ad-LacZ and PBS groups (all P < 0.01).</p><p><b>CONCLUSIONS</b>The TFPI gene could be effectively transferred by adenovirus vector to injured carotid arteries and transferred Ad-TFPI could significantly attenuate intimal proliferation in balloon injured carotid arteries in rabbits.</p>

Combined use of optical coherence tomography and intravascular ultrasound during percutaneous coronary intervention in patients with coronary artery disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the value of combined optical coherence tomography (OCT) and intravascular ultrasound (IVUS) examinations in detecting coronary artery plaque during percutaneous transluminal coronary intervention (PCI).</p><p><b>METHODS</b>OCT and IVUS examinations were performed on 30 diseased coronary vessels from 27 patients underwent PCI from Feb. 2008 to July. 2008.</p><p><b>RESULTS</b>Seventeen vulnerable plaques (4 intima tearing which were not detected by IVUS), 5 plaque rupture (1 out of 5 was detected by IVUS), 5 thrombus lesions (1 out of 5 was found by IVUS), 12 thin-cap lipid-rich lesions (2 detected by IVUS) were detected by OCT in 22 lesions (without 8 lesions post DES stents). Analysis result of plaque burden by IVUS was superior to that obtained by OCT. In 8 DES stents (implanted for 6 months to 4 years), OCT detected 2 had severe restenosis, 6 stents struts were completely covered with neointima without restenosis, 1 stent had aneurysm-like dilatation. IVUS results were similar except for limitations on exactly detecting neointima post stenting. In 19 newly implanted stents, the incidence of stent under-expansion detected by OCT was 26.0% (same as that by IVUS), stent malposition was 63.2% (10.5% by IVUS, P < 0.01), near stent tearing was 10.5% (not detected by IVUS), tissue prolapse between coronary stent struts was 52.6% (10.5% in IVUS, P < 0.05).</p><p><b>CONCLUSIONS</b>OCT imaging is superior to IVUS on detecting vulnerable plaques and change of structure around stents while IVUS is superior to OCT on estimating plaque burden in patients underwent PCI.</p>

CXCL12 Chemokine Mediates Mesenchymal Stem Cell Adhesion and Proliferation Through ?_V and ?_3 Integrins / 中国生物工程杂志

Background The identification of mesenchymal stem cells(MSCs) have provided exciting prospects for cell-based regeneration after myocardic infraction.However cell therapy have inherent limitations such as low survival rate of transplanted cells and insufficient cell number.It is known that cell-matrix adhesion plays a key role in cell proliferation,differentiation and survival,and chemokine CXCL12 may involved in these prcesses.Transfected mesenchymalstem cells with CXCL12 for local secretion of CXCL12 and then explored CXCL12 triggered adhesion of mesenchymal stem cells to extracellular matrix proteins.Mesenchymal stem cells was transfected with CXCL12.?V and ?3 integrins content was evaluated by Western blot analysis.Cell adhesion to extracellular matrix was examined in vitro and cell prolife-ration after transplantation in vivo.Transfection of CXCL12 resulted increased CXCL12 in situ.Increased CXCL12 induced elevated adhesion to fibronectin in vitro and higher survival in vivo.CXCL12 mediated adhesion and proliferation was established by ?V and ?3 integrin subunits.Chemoattractive mechanisms are involved in adhesion processes of mesenchymal stem cells.Increased CXCL12 leads to enhanced expression of ?V and ?3 integrins,which may augment cell survival,proliferation and differrentiation.