Guangqi Chang

MicroRNA-21 Regulates Vascular Smooth Muscle Cell Function via Targeting Tropomyosin 1 in Arteriosclerosis Obliterans of Lower Extremities

Objective —The goal of this study was to determine the expression signature and the potential role of microRNAs in human arteries with arteriosclerosis obliterans (ASO). Methods and Results —The expression profiles of microRNAs in human arteries with ASO and in normal control arteries were determined by quantitative reverse transcription–polymerase chain reaction array. Among the 617 detected microRNAs, multiple microRNAs were aberrantly expressed in arteries with ASO. Some of these dysregulated microRNAs were further verified by quantitative reverse transcription–polymerase chain reaction. Among them, microRNA-21 (miR-21) was mainly located in arterial smooth muscle cells (ASMCs) and was increased by more than 7-fold in ASO that was related to hypoxia inducible factor 1-&agr;. In cultured human ASMCs, cell proliferation and migration were significantly decreased by inhibition of miR-21. 3′-Untranslated region luciferase assay confirmed that tropomyosin 1 was a target of miR-21 that was involved in miR-21-mediated cellular effects, such as cell shape modulation. Conclusion —The results suggest that miR-21 is able to regulate ASMC function by targeting tropomyosin 1. The hypoxia inducible factor-1 &agr;/miR-21/tropomyosin 1 pathway may play a critical role in the pathogenesis of ASO. These findings might provide a new therapeutic target for human ASO.

MicroRNA Profiling Implies New Markers of Chemoresistance of Triple-Negative Breast Cancer

Objective Triple-negative breast cancer (TNBC) patients with truly chemosensitive disease still represent a minority among all TNBC patients. The aim of the present study is to identify microRNAs (miRNAs) that correlate with TNBC chemoresistance. Methods In this study, we conducted miRNAs profile comparison between triple-negative breast cancer (TNBCs) and normal breast tissues by microRNA array. Quantitative real-time PCR (qRT-PCR) was utilized to confirm the specific deregulated miRNAs change trend. We used starBase 2.1 and GOrilla to predict the potential targets of the specific miRNAs. Cells viability and apoptosis assays were employed to determine the effect of alteration of the specific miRNAs in TNBC cells on the chemosensitivity. Results We identified 11 specific deregulated miRNAs, including 5 up-regulated miRNAs (miR-155-5p, miR-21-3p, miR-181a-5p, miR-181b-5p, and miR-183-5p) and 6 down-regulated miRNAs (miR-10b-5p, miR-451a, miR-125b-5p, miR-31-5p, miR-195-5p and miR-130a-3p). Thereafter, this result was confirmed by qRT-PCR. We predicted the potential targets of the candidate miRNAs and found that they are involved in cancer-associated pathways. For the first time, we found that miR-130a-3p and miR-451a were down-regulated in TNBC. 9 of the 11 specific deregulated miRNAs were found to be associated with chemoresistance. In vitro assays, we found that up-regulation of either miR-130a-3p or miR-451a in MDA-MB-231 cells significantly changed the cells sensitivity to doxorubicin. The results suggest that TNBC chemotherapy might be affected by a cluster of miRNAs. Conclusion The abnormal expression miRNAs in TNBC are mainly chemoresistance related. This might be part of reason that TNBC likely to evade from chemotherapy resulting in early relapse and high risk of death. To alter their expression status might be a potential therapeutic strategy to improve the outcome of chemotherapy for TNBC patients.

Endovascular Stenting of Extracranial Carotid Artery Aneurysm: A Systematic Review

OBJECTIVE The objective of this study was to systematically review all available published data about endovascular stenting for patients with extracranial carotid artery aneurysm (ECAA). METHODS All clinical reports in the English language on endovascular stenting for ECAA from 1995 through 2010 were identified. General clinical information, aetiology and parameter of carotid artery aneurysm, information regarding devices, indications for endovascular stenting and in-hospital and follow-up data of each patient were extracted individually. RESULTS A total of 113 studies, involving a total of 224 patients, were included. Procedure success was reported in 92.8% of patients. Postoperative endoleak was reported in 8.1% of patients. The incidence of stroke was 1.8%. Cranial nerve injury occurred in 0.5%. Overall in-hospital mortality was 4.1%. The mean follow-up was 15.4 ± 15.3 months. Stent-graft patency rate was 93.2%. CONCLUSION Endovascular stenting is technically feasible with high procedure success and relatively low complication rate in patients with ECAA. Both short- and mid-term outcomes appear to be favourable.

Calcium carbonate/CaIP6 nanocomposite particles as gene delivery vehicles for human vascular smooth muscle cells

Gene therapy provides great opportunities for treating diseases from genetic disorders to immune system diseases and cancer. Much work has focused on bioactive macromolecules and nanoparticles, which can interact with low-molecular-mass drugs or DNA molecules to form complexes, and have been used for local delivery of therapeutic factors for tissue regeneration or gene therapy. In this study, inorganic amorphous calcium carbonate (ACC) hybrid nanospheres functionalized with a small amount of Ca(II)-IP6 compound (CaIP6) were prepared on a large scale by a facile gas-diffusion method. The results of in vitro transfection experiments show that the obtained functional calcium carbonate/phosphate nanocomposite particles had higher transfection efficiency and lower cytotoxicity level than commercial Lipofectamine 2000. From these results alternative new vectors for gene delivery could be developed. In addition, functionalized inorganic nanocomposite particles are biocompatible and biodegradable, thus the as-prepared hybrid nanospheres are promising for biomedical applications as a safe biomaterial.

Endovascular Stent-graft Treatment for Stanford Type A Aortic Dissection

OBJECTIVE The aim of the study is to summarise our experience of endovascular stent grafting for Stanford type A aortic dissection. DESIGN Retrospective analysis at single centre. METHODS From January 2001 to January 2009, we treated 45 cases of Stanford type A aortic dissection with endovascular stent grafting. The entry tear was located at the ascending aorta in 10 cases (DeBakey type I), the aortic arch in 14 cases and the distal aortic arch or proximal descending aorta in 21 cases in which the ascending aorta was also involved by the dissection. RESULTS The surgical success rate was 97.8% (44/45) and 30-day mortality rate was 6.7% (3/45). Type I endoleaks occurred in 10 cases: one patient died intra-operatively, four were successfully treated with ballooning, four were sealed with aortic cuffs and one case caused by left subclavian artery (LSA) reflux was sealed with an occluder. Average follow-up time was 35.5 ± 5.4 months. Up to the most recent review or death, 32 patients had complete thrombosis and 10 had partial thrombosis inside the false lumen. Two deaths occurred after 30-days postoperatively. CONCLUSION Endovascular stent-graft treatment is a minimally invasive and effective method to treat Stanford type A aortic dissection.

Endovascular treatment of arch and proximal thoracic aortic lesions.

OBJECTIVE To analyze at one institution the endovascular treatment for aortic arch and proximal thoracic aortic lesions, categorize open arch reconstruction, and make preliminary recommendations based on pathology (dissection vs aneurysm), and anatomical extent of disease. METHODS A retrospective review of aortic arch and descending thoracic aortic lesions managed with endovascular treatment between June 2002 and June 2007. RESULTS Thirty-four patients received endovascular repair for aortic dissection (n = 28) and aneurysm (n = 6). Open supra-aortic transposition or debranching of the great vessels was performed in 14 cases of dissection (50%) and six cases (100%) of aneurysm. In 14 dissections, the entry tear was located in the distal aortic arch, enabling the left subclavian artery to be sealed without reconstruction. The procedures were successful in 33 patients (97.1%); one intraoperative death occurred. Type I endoleaks were found intraoperatively in eight cases. After management with balloon angioplasty and by extending the stent implantation, the endoleaks resolved in four cases and decreased in four cases. One patient with Stanford type A dissection died from an unknown cause 3 months after treatment. The overall survival rate was 94.1% (32/34), and all bypass grafts remained patent during the follow-up period. CONCLUSIONS Endovascular stent grafting is a safe and effective method for the treatment of aortic arch lesions. Transposition of the supra-aortic great vessels can be effectively combined with endovascular stent grafting to ensure both cerebral blood supply and enough landing area for the stent graft.

Promising plasmid DNA vector based on APTES-modified silica nanoparticles

Nanoparticles have an enormous potential for development in biomedical applications, such as gene or drug delivery. We developed and characterized aminopropyltriethoxysilane-functionalized silicon dioxide nanoparticles (APTES-SiNPs) for gene therapy. Lipofectamine® 2000, a commonly used agent, served as a contrast. We showed that APTES-SiNPs had a gene transfection efficiency almost equal to that of Lipofectamine 2000, but with lower cytotoxicity. Thus, these novel APTES-SiNPs can achieve highly efficient transfection of plasmid DNA, and to some extent reduce cytotoxicity, which might overcome the critical drawbacks in vivo of conventional carriers, such as viral vectors, organic polymers, and liposomes, and seem to be a promising nonviral gene therapy vector.

MicroRNA-1298 is regulated by DNA methylation and affects vascular smooth muscle cell function by targeting connexin 43

AIMS Growing evidence links microRNA to the process of peripheral vascular disease. Recently, we have found that microRNA-1298(miR-1298) is one of the most significantly down-regulated microRNAs in human arteries with arteriosclerosis obliterans (ASO) of the lower extremities. However, little is known regarding its role in the process of ASO. The present study aimed to investigate the expression, regulatory mechanisms, and functions of miR-1298 in the process of ASO. METHODS AND RESULTS Using quantitative reverse-transcription PCR and in situ hybridization assays, miR-1298 was observed predominantly expressed in the vascular smooth muscle cells (VSMCs) and was significantly down-regulated in ASO compared with normal arteries. Pyrosequencing analysis revealed that the miR-1298 DNA upstream of CpG sites were hypermethylated in ASO compared with normal arteries. Next, the luciferase reporter assay revealed that miR-1298 down-regulation is related with upstream DNA CpG site hypermethylation. Introducing a miR-1298 mimic into cultured VSMCs significantly attenuated cell proliferation and migration. Connexin 43 (Cx43) was validated to be a functional target of miR-1298 that was involved in the miR-1298-mediated cellular effects. Finally, lentivirus-mediated delivery of miR-1298 and its target Cx43 into a rat carotid balloon injury model indicated that re-overexpression of miR-1298 significantly decreased neointimal formation by targeting connexin 43. CONCLUSION Our data demonstrate a specific role of the upstream DNA methylation/miR-1298/Cx43 pathway in regulating VSMC function and suggest that modulation of miR-1298 levels may offer a novel therapeutic approach for ASO.

Management of Acute Mesenteric Ischemia A Critical Review and Treatment Algorithm

Background: Acute mesenteric ischemia (AMI) due to a sudden loss or decrease in blood perfusion to the mesentery represents a highly lethal condition. However, the optimal surgical management remains debatable and merits a more clear recommendation based on a higher level of evidence. Methods: A systematic review of articles published between 2000 and 2013 was performed. Patients were divided into endovascular treatment (ET), open surgery (OS), and hybrid technique (HT) groups. Data of patients’ demographics, procedural information, clinical outcomes including mortality, morbidity, primary patency rate, technique success, primary intestinal resection rate, and second-look laparotomy rate, and follow-up were all retrieved. Comparison between the ET and the OS groups was made using 2-sided Student t test and 2-sided χ2 test or Fisher exact test where appropriate. Results: Twenty-eight articles with a total of 1110 patients were included for the review. The ET group had lower in-hospital mortality and morbidity but similar survival rate during follow-up compared to the OS group. The primary patency rate was higher in the ET group. The overall bowel resection rate was lower in the ET group, and nearly every patient in the cohort who required second-look laparotomy required bowel resection. The HT group seemed to have the lowest mortality and acceptable second-look laparotomy rate and morbidity. Comparison between the HT group and other groups was not possible due to the limited number of cases available for review. Conclusion: Endovascular treatment may serve as a first-line therapy for select patients when there is a low suspicion for intestinal necrosis. Open surgery should be reserved for emergency conditions requiring exploratory laparotomy. Hybrid technique may be an especially effective approach for treating AMI, with low morbidity and mortality, although further studies are required comparing it to OS and ET.

Initial and Middle-Term Outcome of Treatment for Spontaneous Isolated Dissection of Superior Mesenteric Artery.

AbstractSymptomatic isolated dissection of the superior mesenteric artery (SIDSMA) represents an extremely rare condition. Although various treatments including conservative treatment, endovascular stenting (ES), and surgical repair are currently available, consensus treatment guideline is absent due to scarce of SIDSMA cases. Thus, we present our experience in the treatment of SIDSMA at our single center.Fourteen cases of SIDSMA were treated with conservative treatment, catheter-directed thrombolysis (CDT), endovascular stenting (ES), or surgical repair at our center between January 2008 and January 2014. Demographics, clinical manifestations, coexisting medical conditions, imaging feature, treatments, and follow-up outcome of these patients were retrospectively collected and analyzed.For 13 patients without peritonitis, conservative treatment was given for 4 to 6 days initially. After the first observation cycle, symptoms and signs were alleviated in 8 patients, and conservative treatments were continued. The remaining 5 patients received technically and clinically successful ES (in 4) or CDT (in 1) due to worsening symptoms and signs during conservative treatment. One patient with peritonitis underwent emergency surgery, with the necrotic small intestine resected. However, the abdominal pain was not alleviated 17 days postoperatively, ES was thus performed and symptoms relieved immediately. Two weeks after ES, a new aneurysm and partial thrombosis in the distal part of the stent were found by computed tomography angiography in this patient. No intestinal infarction or mortality developed during hospitalization. Follow-up was accomplished in 11 cases, ranging from 4 to 74 months (23.5 ± 21.3). Except that one complained with mild abdominal pain, the other 10 achieved complete remission. All patients were free from new aneurysmal formation of SMA and all stents remained patent.For SIDSMA without peritonitis, conservative treatment can be provided with reasonable success rate, while ES may serve as an effective alternative once conservative treatment fails. For SIDSMA with peritonitis, open surgery remains the treatment of choice by resection of necrotic intestine and revasculization.