Coronary thrombolysis with recombinant tissue-type plasminogen activator: Patency rate and regional wall motion after 3 months

In a double-blind, placebo-controlled, randomized trial the long-term (± 3 months) effects of intravenous administration of recombinant tissue-type plasminogen activator (rt-PA) versus placebo were compared in relation to left ventricular function, coronary patency rate and antigenicity in 28 patients with a first myocardial infarction. Patency rate of the infarct-related coronary artery at the end of the rt-PA/placebo infusion and after 3 months of medical treatment (including oral anticoagulant agents) was 86 and 71%, respectively, in the rt-PA group, and 21 and 58%, respectively, in the placebo group.Regional wall motion of the infarct-related area was quantitated with digital subtraction angiography. Intra-patient comparisons revealed significant improvement in regional wall motion after 3 months in both the rt-PA and placebo groups. The improvement in the rt-PA group was not significantly greater than that in the placebo group. Thirteen patients (10 with rt-PA and 3 with placebo) with persistent patency (both early and late) of the infarct-related coronary artery showed a significant improvement of both global and regional left ventricular function, while 8 patients (2 with rt-PA and 6 with placebo) with persistent occlusion showed no changes. Antibodies against rt-PA were not detected in serum 2 weeks after the infusion, which is indicative of the lack of antigenicity of rt-PA and allows for its repeated administration

CORRELATION BETWEEN LEUKOCYTE TELOMERE LENGTH AND DRUG ELUTING STENT STRUT COVERAGE BY OPTICAL COHERENCE TOMOGRAPHY

El cementiri de Sant Andreu fou inaugurat el 1839 i pertanyia a Sant Andreu del Palomar que formava part del Pla de Barcelona. Sembla que fou la primera població del Pla que va disposar de cementiri desprès de la construcció del de Poblenou

Cordycepin promotes apoptosis by modulating the ERK-JNK signaling pathway via DUSP5 in renal cancer cells

Constitutive activation of extracellular signal regulated kinase (ERK)-Jun NH2-terminal kinase (JNK) signaling commonly occurs in tumors. The activation of ERK promotes cell proliferation, whereas that of JNK induces cell apoptosis. However, the apoptotic mechanism of ERK-JNK signaling in cancer is not well understood. Recently, we identified that apoptosis and activation of the JNK signaling pathway were induced after cordycepin treatment in human renal cancer, suggesting that JNK signaling might contribute to TK-10 cell apoptosis. We investigated the apoptotic effects of cordycepin by evaluating the activation of the ERK-JNK signaling pathway in renal cancer TK-10 cells. We found that cordycepin downregulated ERK and DUSP5, upregulated phosphorylated-JNK (p-JNK), and induced apoptosis. Moreover, we showed that siRNA-mediated inhibition of ERK downregulated DUSP5, whereas ERK overexpression upregulated DUSP5, and that DUSP5 knockdown by siRNA upregulated p-JNK. The JNK-specific inhibitor SP600125 upregulated nuclear translocation of β-catenin, and downregulated Dickkopf-1 (Dkk1), which has been shown to be a potent inhibitor of Wnt signaling. Dkk1 knockdown by siRNA upregulated nuclear β-catenin, suggesting the involvement of the Wnt/β-catenin signaling pathway. DUSP5 overexpression in TK-10 cells decreased p-JNK and increased nuclear β-catenin. The decreased Bax activation markedly protected against cordycepin-induced apoptosis. Bax subfamily proteins induced apoptosis through caspase-3. Taken together, we show that JNK signaling activation by cordycepin mediated ERK inhibition, which might have induced Bax translocation and caspase-3 activation via regulation of DUSP5 in TK-10 cells, thereby promoting the apoptosis of TK-10 cells. Targeting ERK-JNK signaling via the apoptotic effects of cordycepin could be a potential therapeutic strategy to treat renal cancer

Cordycepin induces apoptosis by caveolin-1-mediated JNK regulation of Foxo3a in human lung adenocarcinoma

Forkhead transcription factor (Foxo3a) is a downstream effector of JNK-induced tumor suppression. However, it is not clear whether the caveolin-1 (CAV1)-mediated JNK/Foxo3a pathway is involved in cancer cell apoptosis. We found that cordycepin upregulates CAV1 expression, which was accompanied by JNK phosphorylation (p-JNK) and subsequent Foxo3a translocation into the nucleus, resulting in the upregulation of Bax protein expression. Furthermore, we found that CAV1 overexpression upregulated p-JNK, whereas CAV1 siRNA downregulated p-JNK. Additionally, SP600125, a specific JNK inhibitor, significantly increased Foxo3a phosphorylation, which downregulated Foxo3a translocation into the nucleus, indicating that CAV1 mediates JNK regulation of Foxo3a. Foxo3a siRNA downregulated Bax protein and attenuated A549 apoptosis, indicating that the CAV1-mediated JNK/Foxo3a pathway induces the apoptosis of A549 lung cancer cells. Cordycepin significantly decreased tumor volume in nude mice. Taken together, these results indicate that cordycepin promotes CAV1 upregulation to enhance JNK/Foxo3a signaling pathway activation, inducing apoptosis in lung cancer cells, and support its potential as a therapeutic agent for lung cancer

Comparison between Integrated Backscatter Intravascular Ultrasound and 64-Slice Multi-Detector Row Computed Tomography for Tissue Characterization and Volumetric Assessment of Coronary Plaques

Background: The purpose of this study was to determine the cut-off values of Hounsfield units (HU) for the discrimination of plaque components and to evaluate the feasibility of measurement of the volume of plaque components using multi-detector row computed tomography (MDCT). Methods: Coronary lesions (125 lesions in 125 patients) were visualized by both integrated backscatter intravascular ultrasound (IB-IVUS) and 64-slice MDCT at the same site. The IB values were used as a gold standard to determine the cut off values of HU for the discrimination of plaque components. Results: Plaques were classified as lipid pool (n =50), fibrosis (n =65) or calcification (n =35) by IB-IVUS. The HU of lipid pool, fibrosis and calcification were 18 ± 18 HU (−19 to 58 HU), 95 ± 24 HU (46 to 154 HU) and 378 ± 99 HU (188 to 605 HU), respectively. Using receiver operating characteristic curve analysis, a threshold of 50 HU was the optimal cutoff values to discriminate lipid pool from fibrosis. Lipid volume measured by MDCT was correlated with that measured by IB-IVUS (r =0.66, p <0.001), whereas fibrous volume was not (r =0.21, p =0.059). Conclusion: Lipid volume measured by MDCT was moderately correlated with that measured by IB-IVUS. MDCT may be useful for volumetric assessment of the lipid volume of coronary plaques, whereas the assessment of fibrosis volume was unstable

Differences in coronary plaque characteristics between patients with and those without peripheral arterial disease.

INTRODUCTION Cardiovascular mortality of patients with combined peripheral arterial disease (PAD) and coronary artery disease (CAD) is twice as high as that in those with either disease alone. It is known that patients with PAD undergoing percutaneous coronary intervention have a higher incidence of adverse cardiac events such as myocardial infarction or target vessel revascularization. OBJECTIVE In this study, we compared the detailed characteristics of culprit and nonculprit plaques between patients with and those without PAD using optical coherence tomography. PATIENTS AND METHODS We performed propensity score matching using the following variables: (i) age; (ii) sex; (iii) clinical presentation; (iv) diabetes mellitus; (v) hyperlipidemia; (vi) smoking; (vii) hypertension; (viii) BMI; and (ix) coronary lesion location. Finally, we matched 34 culprit lesions and 30 nonculprit lesions in patients with PAD to 68 culprit lesions and 60 nonculprit lesions in patients without PAD (1 : 2 ratio). RESULTS In culprit lesions, PAD patients when compared with those without PAD had a higher prevalence of lipid-rich plaque (73.5 vs. 51.5%; P=0.033), higher lipid index (1744±1110 vs. 1246±656; P=0.043), calcification (79.4 vs. 58.8%; P=0.039), macrophage accumulation (70.6 vs. 48.5%; P=0.034), and cholesterol crystals (32.4 vs. 10.3%; P=0.006). In nonculprit lesions, PAD patients had a higher prevalence of calcification (76.7 vs. 55.0%; P=0.046), macrophage accumulation (63.3 vs. 38.3%; P=0.025), and cholesterol crystals (36.7 vs. 16.7%; P=0.034). CONCLUSION Our study suggests greater coronary plaque vulnerability in both culprit and nonculprit lesions in patients with PAD. This observation underscores the need for more aggressive risk management in patients with combined PAD and coronary artery disease

Evaluation in 3 Months Duration of Neointimal Coverage After Zotarolimus-Eluting Stent Implantation by Optical Coherence Tomography The ENDEAVOR OCT Trial

ObjectivesWe performed this study to investigate the vascular response in early period after zotarolimus-eluting stent (ZES) (Endeavor Sprint, Medtronic CardioVascular, Minneapolis, Minnesota) implantation.BackgroundThe ZES has different characteristics, with biocompatible polymer and rapid drug-elution, compared with the first-generation drug-eluting stents (DES).MethodsThe ENDEAVOR OCT (Evaluation in 3 Months Duration of Neointimal Coverage after Zotarolimus-Eluting Stent Implantation by Optical Coherence Tomography) trial is a prospective, single-center study evaluating vascular healing patterns with optical coherence tomography (OCT) at 3 months after stent implantation. A total of 31 ZES in 30 patients underwent serial OCT at immediate post-intervention and 3 months. Neointimal growth and malapposition were analyzed at each stent strut of cross-sectional OCT images with 0.5-mm intervals.ResultsThe incidence of malapposition at post-intervention and 3 months was 6.0% and 0.2%, respectively. However, late acquired malapposition was not detected at 3 months. Of 31 stents, 27 stents (87.1%) were covered completely with neointima, but the remaining 4 stents had 2 (0.8%), 4 (0.9%), 4 (1.2%), and 6 (1.4%) uncovered struts. Overall mean percentage of covered stent struts was 99.9 ± 0.4%. This finding was consistent among groups with acute coronary syndrome and stable angina pectoris (99.9 ± 0.3% vs. 99.9 ± 0.4%, p = 0.92). Intracoronary thrombus was documented in 1 stent (3.2%) among 31 stents.ConclusionsMost of the stent struts were covered with neointima, and late acquired malapposition was not found at 3 months after ZES implantation. Therefore, the current study demonstrated that ZES might have a favorable in vivo vascular response at 3 months after stent implantation. (Evaluation of Zotarolimus Eluting Stent at 3 Months Using Optical Coherence Tomography [ENDEAVOR OCT]; NCT00815139

Role of Lipid-Lowering and Anti-Inflammatory Therapies on Plaque Stabilization

Atherosclerosis is the predominant underlying etiopathology of coronary artery disease. Changes in plaque phenotype from stable to high risk may spur future major adverse cardiac events (MACE). Different pharmacological therapies have been implemented to mitigate this risk. Over the last two decades, intravascular imaging modalities have emerged in clinical studies to clarify how these therapies may affect the composition and burden of coronary plaques. Lipid-lowering agents, such as statins, ezetimibe, and proprotein convertase subtilisin/kexin type 9 inhibitors, were shown not only to reduce low-density lipoprotein levels and MACE but also to directly affect features of coronary plaque vulnerability. Studies have demonstrated that lipid-lowering therapy reduces the percentage of atheroma volume and number of macrophages and increases fibrous cap thickness. Future studies should answer the question of whether pharmacological plaque stabilization may be sufficient to mitigate the risk of MACE for selected groups of patients with atherosclerotic coronary disease.</p