Dedicator of cytokinesis 2 silencing therapy inhibits neointima formation and improves blood flow in rat vein grafts.

OBJECTIVE: The high rate of vein graft failure due to neointimal hyperplasia is a major challenge for cardiovascular surgery. Finding novel approaches to prevent neointimal hyperplasia is important. Thus, the purpose of this study was to investigate whether dedicator of cytokinesis 2 (DOCK2) plays a role in the development of neointima formation in the vein grafts. METHODS AND RESULTS: We found that DOCK2 levels were significantly elevated in the vein grafts following grafting surgery. In addition, overexpression of DOCK2 promoted venous smooth muscle cell (SMC) proliferation and migration. Conversely, knocking-down endogenous DOCK2 expression in venous SMCs inhibited SMC proliferation and migration. Consistent with this, knocking-down DOCK2 expression in the grafted veins significantly reduced neointimal formation compared with the controls 28 days after vein transplantation. Moreover, DOCK2 silencing treatment improved hemodynamics in the vein grafts. Mechanistically, knockdown of DOCK2 significantly alleviated the vein graft-induced down regulation of SMC contractile protein expression and impeded the vein graft-induction of both Cyclin D1 and PCNA expression. In particular, to ensure high efficiency when transferring the DOCK2 short hairpin RNA (shDOCK2) into the grafted veins, a 30% poloxamer F-127 gel incorporated with 0.25% trypsin was smeared around the vein grafts to increase the adenovirus contact time and penetration. CONCLUSIONS: DOCK2 silencing gene therapy effectively attenuates neointimal hyperplasia in vein grafts. Knock-down of DOCK2 would be a potential therapeutic approach for the treatment of vein graft failure.

MicroRNA-365 promotes the contractile phenotype of venous smooth muscle cells and inhibits neointimal formation in rat vein grafts.

The high rate of autologous vein graft failure caused by neointimal hyperplasia remains an unresolved issue in the field of cardiovascular surgery; therefore, it is important to explore new methods for protecting against neointimal hyperplasia. MicroRNA-365 has been reported to inhibit the proliferation of vascular smooth muscle cells (SMCs). This study aimed to test whether adenovirus-mediated miR-365 was able to attenuate neointimal formation in rat vein grafts. We found that miR-365 expression was substantially reduced in vein grafts following engraftment. In vitro, overexpression of miR-365 promoted smooth muscle-specific gene expression and inhibited venous SMC proliferation and migration. Consistent with this, overexpression of miR-365 in a rat vein graft model significantly reduced grafting-induced neointimal formation and effectively improved the hemodynamics of the vein grafts. Mechanistically, we identified that cyclin D1 as a potential downstream target of miR-365 in vein grafts. Specially, to increase the efficiency of miR-365 gene transfection, a 30% poloxamer F-127 gel containing 0.25% trypsin was mixed with adenovirus and spread around the vein grafts to increase the adenovirus contact time and penetration. We showed that adenovirus-mediated miR-365 attenuated venous SMC proliferation and migration in vitro and effectively inhibited neointimal formation in rat vein grafts. Restoring expression of miR-365 is a potential therapeutic approach for the treatment of vein graft failure. © 2019 IUBMB Life, 2019.

MicroRNA-146a sponge therapy suppresses neointimal formation in rat vein grafts.

The long-term failure of vein grafts due to neointimal hyperplasia remains a difficult problem in cardiovascular surgery. Exploring novel approaches to prevent neointimal hyperplasia is important. MicroRNA-146a (miR-146a) plays an essential role in promoting vascular smooth muscle cell (VSMC) proliferation. Thus, the aim of the present study is to investigate whether adenovirus-mediated miR-146a sponge (Ad-miR-146a-SP) gene therapy could attenuate neointimal formation in rat vein grafts. (Ad-miR-146a-SP) was constructed to transfect cultured VSMCs and grafted veins. To improve the efficiency of transferring the miR-146a sponge gene into the grafted veins, 20% poloxamer F-127 gel incorporated with 0.25% trypsin was used to increase adenovirus contact time and penetration. miR-146a-SP transduction significantly reduced the expression of miR-146a both in cultured VSMCs and vein grafts. miR-146a sponge markedly attenuated VSMC proliferation and migration. Consistent with this, miR-146a sponge gene therapy significantly attenuated neointimal formation and also improved blood flow in the vein grafts. Mechanistically, we identified the Krüppel-like factor 4(KLF4) as a potential downstream target gene of miR-146a in vein grafts. Our data show that miR-146a sponge gene therapy could effectively reduce miR-146a activity and attenuate neointimal formation in vein grafts, suggesting its potential therapeutic application for prevention of vein graft failure. © 2018 IUBMB Life, 71(1):125-133, 2019.

Research on the Temperature Characteristics of the Photoacoustic Sensor of Glucose Solution.

In order to weaken the influence of temperature on photoacoustic (PA) measurements and compensate PA signals with a proposed theoretical model, the relationship of PA signal amplitude with temperature, under the condition of different glucose concentrations and different light intensities, was studied in this paper. First, the theoretical model was derived from the theory of the PA effect. Then, the temperature characteristics of the PA signals were investigated, based on the analyses of the temperature-dependent Grüneisen parameter in glucose solution. Next, the concept of a PA temperature coefficient was proposed in this paper. The result of the theoretical analysis shows that this coefficient is linear to light intensity and irrelevant to the concentration of glucose solution. Furthermore, a new concept of a PA temperature coefficient of unit light intensity was proposed in this paper. This coefficient is approximately constant, with different light intensities and solution concentrations, which is similar to the thermal expansion coefficient. After calculation, the PA temperature coefficient by the unit light intensity of glucose solution is about 0.936 bar/K. Finally, relevant experiments were carried out to verify the theoretical analysis, and the PA temperature coefficient of the unit light intensity of glucose solution is about 0.04/°C. This method can also be used in sensors measuring concentrations in other aqueous solutions.

[Effect of intensity modulated radiation therapy on oral mucosa and immune function in patients with nasopharyngeal carcinoma].

OBJECTIVE: To study the potential effects of intensity modulated radiation therapy (IMRT) on clinical efficacy, oral mucosa reaction and immunological foundation; and to explore the effect of immunological changes on clinical efficacy and oral mucosa reaction in patients with nasopharyngeal carcinoma.
 Methods: A total of 200 patients with nasopharyngeal carcinoma, who came from First Department of Nasopharyngeal Radiotherapy, the First People's Hospital of Foshan from October 2008 to November 2011, were selected. The patients were treated with nasopharyngeal radiotherapy, and divided into an observation group and a control group (n=100 in each group). The control group underwent common conventional two-dimensional radiotherapy treatment, while the observation group underwent IMRT. The 5-year survival rates and recurrence rates were recorded at follow-up. After the radiotherapy, the oral mucosa in the patients were evaluated by the classification standard of acute radioactive mucositis by American Radiotherapy Oncology Group (RTOG), and the number of T lymphocyte subsets before and after treatment was detected.
 Results: There were significant difference in non-regional-recurrence survival rate, disease-free survival rate, local recurrence rate between the above 2 groups (all P<0.05), but no significant difference in the distant metastasis-free survival rate (P>0.05). The acute oral mucosa reactions of grade 1, 2, 3, 4 in the control group were 8.00%, 20.00%, 12.00%, 7.00%, respectively, and those were 7.00%, 22.00%, 15.00%, 1.00% respectively. There was no significant difference in the acute response of oral mucosa in grade 1, 2 and 3 in the 2 groups (all P>0.05), but there was significant difference in the grade 4 (P<0.05). There were significantly difference in CD8+, CD4+/ CD8+ and CD4+ T lymphocyte subsets before and after treatment in the above 2 groups (all P<0.01); there were also significantly difference after treatment between the observation group and the control group (all P<0.01).
 Conclusion: In the process of treatment in patients with nasopharyngeal carcinoma, the use of IMRT on the basis of chemotherapy is more effective than the conventional two-dimensional radiotherapy, which can reduce the proportion of grade 4 (severe) acute oral mucosa reaction. It may be related to the protective effect of IMRT on immune function in the patients.

Plasma levels of high mobility group box 1 increase in patients with posttraumatic stress disorder after severe blunt chest trauma: a prospective cohort study.

BACKGROUND: High-mobility group box 1 (HMGB1), a key late mediator of systemic inflammation, is a potentially useful biomarker for predicting outcome in patients with severe blunt chest trauma. The purpose of this study was to define the relationship between plasma levels of HMGB1 and posttraumatic stress disorder (PTSD) in patients with severe blunt chest trauma. METHODS: All patients with severe blunt chest trauma (abbreviated injury score ≥3) who were admitted to traumatic surgery department and ultimately survived to follow-up at 6 mo were eligible for the study. HMGB1 was sampled every other day from day 1-day 7 after admission, and plasma concentrations of HMGB1 were measured by a quantitative enzyme-linked immunosorbent assay test. Multivariate regression analysis was used to define the independent contribution of possible risk factors selected by univariate analysis. RESULTS: PTSD was identified in 43 patients including acute PTSD (n = 21), chronic PTSD (n = 18), and delayed-onset PTSD (n = 4) after 6-mo follow-up, in whom significant higher plasma levels of HMGB1 on days three, five, and seven after blunt chest trauma were noted compared with those seen in patients without PTSD (n = 10). Multivariate logistic analysis showed that transfusion, injury severity score, and HMGB1 levels at day 7 were the valuable risk factors for PTSD. CONCLUSIONS: In blunt chest trauma, plasma HMGB1 levels were significantly higher in patients with PTSD compared with patients with non-PTSD. Our data indicate that patients with high plasma levels of HMGB1 may be more prone to develop PTSD including acute and chronic PTSD.

In vivo degradation of copolymers prepared from L-lactide, 1,3-trimethylene carbonate and glycolide as coronary stent materials.

A series of high molecular weight polymers were prepared by ring opening polymerization of L-lactide (L-LA), 1,3-trimethylene carbonate (TMC) and glycolide using stannous octoate as catalyst. The resulting polymers were characterized by gel permeation chromatography, (1)H nuclear magnetic resonance, differential scanning calorimeter and tensile tests. All the polymers present high molecular weights. Compared with PLLA and PTLA copolymers, the terpolymers exhibit interesting properties such as improved toughness and lowered crystallinity with only slightly reduced mechanical strength. In vivo degradation was performed by subcutaneous implantation in rats to evaluate the potential of the copolymers as bioresorbable coronary stent material. The results show that all the polymers conserved to a large extent their mechanical properties during the first 90 days, except the strain at break which exhibited a strong decrease. Meanwhile, significant molecular weight decrease and weight loss are detected in the case of terpolymers. Therefore, the PTLGA terpolymers present a good potential for the development of totally bioresorbable coronary stents.

[Association between CCND1 G870A polymorphism and radiotherapy response in high-risk human papillomavirus-related cervical cancer].

OBJECTIVE: To investigate the correlation of cyclin D1 (CCND1) G870A single nucleotide polymorphism (SNP) with radiotherapy response in patients with high risk human papillomavirus (HR-HPV) related cervical cancer.
 METHODS: A total of 273 patients with cervical cancer, who were confirmed by histopathology and hybrid capture 2 (HC-2) assay and treated by radiotherapy, were enrolled for this study. The correlation of CCND1 G870A polymorphism with tumor response in patients was assessed.
 RESULTS: Compared with patients with AA genotype, the patients with GG genotype and AA genotype showed lower sensitivity to radio-therapy treatment (adjusted ORGA=2.69, 95% CI 1.28-5.67 and adjusted ORGG=3.28, 95% CI 1.47-7.29, respectively), an increase in risks of recurrence/metastasis (adjusted ORGA=2.52, 95% CI 1.12-5.63 and adjusted ORGG=3.95, 95% CI 1.68-9.26, respectively), and shorter recurrence/metastasis-free survival (PGA=0.010 and PGG=0.045).
 CONCLUSION: G870A polymorphism is a frequent variation that could be used for evaluate the radio-sensitivity and prognosis for patients with HR-HPV related cervical cancer.

Comparative Study of Single Opening&Closing and Continuous Pulsatile Flow Valve Tester.

PURPOSE: The purpose is to demonstrate the difference in closing volume fraction between the single opening&closing valve tester (SOCVT) and continuous pulsatile flow valve tester (CPFVT). METHODS: A comparative study was conducted in four hemodynamic conditions selected from the ISO 5840 on the four mitral valve states: normal annulus, 40% annulus dilation, 60% annulus dilation, and repaired valve with a clip device in both the SOCVT and CPFVT. The closing volume fractions were compared and errors calculated in the 16 cases. RESULTS: In the CPFVT, the flowrate waveform depends more on hemodynamic conditions rather than the valve morphology. For closing volume fractions in the two testers, twelve cases had errors between 10% and 20% and 3 cases had errors between 2.2% and 5.5%. There was no statistic difference in the closing volume fraction between the CPFVT and SOCVT for the normal annulus, 40% valve annulus dilation, 60% valve annulus dilation and repaired valves (P values = 0.44, 0.44, 0.33, and 0.08, respectively, n = 4). CONCLUSION: There is certain error in closing volume measurements, even if no statistic difference in closing volume measured by the SOCVT and CPFVT. The typical flow waveforms of the mitral valve may be available to standardize testing of the SOCVT to evaluate valve hemodynamics. The SOCVT may be an alternative to the valve testing.

Nanopore long-read RNA sequencing reveals functional alternative splicing variants in human vascular smooth muscle cells.

Vascular smooth muscle cells (VSMCs) are the major contributor to vascular repair and remodeling, which showed high level of phenotypic plasticity. Abnormalities in VSMC plasticity can lead to multiple cardiovascular diseases, wherein alternative splicing plays important roles. However, alternative splicing variants in VSMC plasticity are not fully understood. Here we systematically characterized the long-read transcriptome and their dysregulation in  human aortic smooth muscle cells (HASMCs) by employing the Oxford Nanopore Technologies long-read RNA sequencing in HASMCs that are separately treated with platelet-derived growth factor, transforming growth factor, and hsa-miR-221-3P transfection. Our analysis reveals frequent alternative splicing events and thousands of unannotated transcripts generated from alternative splicing. HASMCs treated with different factors exhibit distinct transcriptional reprogramming modulated by alternative splicing. We also found that unannotated transcripts produce different open reading frames compared to the annotated transcripts. Finally, we experimentally validated the unannotated transcript derived from gene CISD1, namely CISD1-u, which plays a role in the phenotypic switch of HASMCs. Our study characterizes the phenotypic modulation of HASMCs from an insight of long-read transcriptome, which would promote the understanding and the manipulation of HASMC plasticity in cardiovascular diseases.

Classification and Segmentation Algorithm in Benign and Malignant Pulmonary Nodules under Different CT Reconstruction.

Methods: The imaging data of 55 patients with chest CT plain scan in the Xuancheng People's Hospital were collected retrospectively. The data of each patient included lung window reconstruction, mediastinum reconstruction, and bone window reconstruction. The depth neural network and 3D convolution neural network were used to construct the model and train the classification and segmentation algorithm. The pathological results were the gold standard for benign and malignant pulmonary nodules. The classification and segmentation algorithms under three CT reconstruction algorithms were compared and analyzed by analysis of variance. Results: Under the three CT reconstruction algorithms, the classification accuracy of pulmonary nodule density types was 98.2%, 96.4%, and 94.5%, respectively. The Dice coefficients of all nodule segmentation were 80.32% ± 5.91%, 79.83% ± 6.12%, and 80.17% ± 5.89%, respectively. The diagnostic accuracy between benign and malignant pulmonary nodules under different reconstruction algorithms was 98.2%, 96.4%, and 94.5%, respectively. There was no significant difference in the classification accuracy, Dice coefficients, and diagnostic accuracy of pulmonary nodules under three different reconstruction algorithms (all P > 0.05). Conclusion: The depth neural network algorithm combined with 3D convolution neural network has a good efficiency in identifying benign and malignant pulmonary nodules under different CT reconstruction classification and segmentation algorithms.

Low-dose AAV-CRISPR-mediated liver-specific knock-in restored hemostasis in neonatal hemophilia B mice with subtle antibody response.

AAV-delivered CRISPR/Cas9 (AAV-CRISPR) has shown promising potentials in preclinical models to efficiently insert therapeutic gene sequences in somatic tissues. However, the AAV input doses required were prohibitively high and posed serious risk of toxicity. Here, we performed AAV-CRISPR mediated homology-independent knock-in at a new target site in mAlb 3'UTR and demonstrated that single dose of AAVs enabled long-term integration and expression of hF9 transgene in both adult and neonatal hemophilia B mice (mF9 -/-), yielding high levels of circulating human Factor IX (hFIX) and stable hemostasis restoration during entire 48-week observation period. Furthermore, we achieved hemostasis correction with a significantly lower AAV dose (2 × 109 vg/neonate and 1 × 1010 vg/adult mouse) through liver-specific gene knock-in using hyperactive hF9R338L variant. The plasma antibodies against Cas9 and AAV in the neonatal mice receiving low-dose AAV-CRISPR were negligible, which lent support to the development of AAV-CRISPR mediated somatic knock-in for treating inherited diseases.

In vivo study on the histocompatibility and degradation behavior of biodegradable poly(trimethylene carbonate-co-D,L-lactide).

The aim of this study was to explore the in vivo behavior and histocompatibility of poly(trimethylene carbonate-co-D,L-lactide) (PDLLA/TMC) and its feasibility of manufacturing cardiovascular stents. Copolymers with 50/50 molar ratio were synthesized by ring-opening polymerization with TMC and D, L-LA, or TMC and L-LA. Poly(L-lactide) (PLLA) was synthesized as a control. The films of the three polymers were implanted into 144 Wistar rats. At different time points of implantation, polymer films were explanted for the evaluation of degradation characteristics and histocompatibility using size exclusion chromatography , nuclear magnetic resonance , environmental scanning electron microscope , and optical microscope. Results showed that there were differences in the percentage of mass loss, molecular weight, shape and appearance changes, and inflammation cell counts between different polymers. With the time extended, the film's superficial structure transformed variously, which was rather obvious in the polymer of PDLLA/TMC. In addition, there were relatively lower inflammation cell counts in the PDLLA/TMC and poly(trimethylene carbonate-co-L-lactide) (PLLA/TMC) groups at different time points in comparison with those in the PLLA group. The differences were of statistical significance (P< 0.05) in the group of PDLLA/TMC vs. PLLA, and the group of PLLA/TMC vs. PLLA, but not within the PDLLA/TMC and PLLA/TMC groups (P> 0.05). These results suggested that the polymer of PDLLA/TMC (50/50) with favorable degradation performance and histocompatibility is fully biodegradable and suitable for manufacturing implanted cardiovascular stents.

In vivo evaluation of a novel dexamethasone-heparin-double-coated stent for inhibition of artery restenosis and thrombosis.

To evaluate the efficacy and safety of dexamethasone-heparin-double-coated stent (DHDCS) on inhibition of artery lumen reduction and neointimal hyperplasia in porcine model we carried out this study. Bare mental stents (BMS, n = 12), protein-coated stents (PCS, n = 12), heparin microballoon-coated stents (HMCS, n = 12), and DHDCS (n = 12), prepared by the spray drying method, were implanted into the selected internal iliac artery, external iliac artery, sacrococcygeal artery, and femoral artery of each of the selected pigs (n = 12), which were randomly divided into four groups on average. Thirty days and ninety days after the implantation, aorta angiography was performed on all the 12 mini-pigs to evaluate the artery lumen reduction. Subsequently, in order to analyze their histological appearance, the pigs were killed, and their arteries with the stents inside were taken out, embedded in plastic for hard histological section and hematoxylin-eosin (H.E.) staining, and examined by light microscopy and scanning electron microscopy (SEM). The artery lumen reduction and average neointimal hyperplasia in the group of DHDCS were significantly lesser than those in the other three groups of BMS, PCS, and HMCS. This study shows that DHDCS is capable of inhibiting the proliferation of intima and lumen area reduction of the target artery within stents, and effectively and safely reducing the incidence of regional thrombosis and restenosis for a short term.

Evaluation of a novel paclitaxel-eluting stent with a bioabsorbable polymeric surface coating in the porcine artery injury model.

PURPOSE: Drug-eluting stents (DES) are unique in allowing sustained release after a single short intervention. The challenge with DES still remaining is the optimal combination of a biocompatible drug-eluting matrix including an antiproliferative drug. We studied the role of a novel paclitaxel-eluting stent with a bioabsorbable polymer coating in preventing vascular restenosis in the porcine artery injury model. MATERIAL AND METHODS: Bare metal stents (BMS); polymer-coated-only stents (POLY); and polymer-based paclitaxel-eluting stents (PACL) were randomly implanted in pig femoral arteries. The dose density of paclitaxel was 1 microg/mm2 with in vitro studies demonstrating a gradual elution over a course of 6 month. RESULTS: After 1-, 3- and 6-month follow-up, respectively, the animals underwent angiographic restudy and were terminated for histomorphometrical and histopathological analyses. At 1 month, the PACL group had the lowest histological percent stenosis when compared to the BMS and POLY groups (20 +/- 4% vs 39 +/- 6% and 41 +/- 6%, respectively, P < 0.05). At 3 months, the PACL group still presents the lowest level of histological percent stenosis among the three groups (27 +/- 6% vs 50 +/- 10% and 46 +/- 5%, respectively, P < 0.01). Six months later, the PACL group showed a similar histological percent stenosis as the BMS and POLY groups (44 +/- 9% vs 56 +/- 11% and 53 +/- 9%, respectively, P = 0.145). CONCLUSIONS: This study shows favourable vascular compatibility and efficacy for a novel DES to inhibit in-stent neointima formation and preserve lumen area in the porcine artery model.

A prospective evaluation of apolipoprotein M gene T-778C polymorphism in relation to coronary artery disease in Han Chinese.

OBJECTIVES: Apolipoprotein M (apoM) is important for the formation of pre-beta-high-density lipoprotein (HDL) and cholesterol efflux in macrophages. It is demonstrated that single-nucleotide polymorphism (SNP) T-778C of apoM gene is related to type 2 diabetes in Han Chinese. In the present study, we investigated the possible association of apoM polymorphism in relation to coronary artery disease (CAD) in Han Chinese. DESIGN AND METHODS: This case-controlled study consisted of 118 CAD patients who were diagnosed angiographically to have at least 30% stenosis, and 255 unrelated subjects who were used as control. ApoM gene polymorphism in the proximal promoter region was analyzed by PCR-RFLP and serum lipid levels were also measured. RESULTS: It is indicated that CAD patients had increased frequency of C allele on apoM T-778C compared to the controls (14.8% vs. 6.9%, P=0.0008). Multivariable logistic regression analysis indicated that odds ratios (ORs) for all subjects with apoM CC+CT genotypes and C allele were 1.9 (95% CI=1.1-2.9, P<0.0001) and 1.9 (95% CI=1.3-3.2, P<0.0001), respectively. The plasma total cholesterol (TC) levels were significantly higher in individuals with CC or CT genotype than those with TT genotype in both CAD patients and controls. CONCLUSIONS: The present findings suggest that the C allele at nucleotide -778 in the apoM gene is a risk factor for genetic susceptibility to CAD and is also associated with TC levels in Han Chinese.

Adenovirus-Mediated Gene Transfer of microRNA-21 Sponge Inhibits Neointimal Hyperplasia in Rat Vein Grafts.

Background: Vein graft failure due to neointimal hyperplasia remains an important and unresolved complication of cardiovascular surgery. microRNA-21 (miR-21) plays a major role in regulating vascular smooth muscle cell (VSMC) proliferation and phenotype transformation. Thus, the purpose of this study was to determine whether adenovirus-mediated miR-21 sponge gene therapy was able to inhibit neointimal hyperplasia in rat vein grafts. Methods: Adenovirus-mediated miR-21 sponge was used to inhibit VSMC proliferation in vitro and neointimal formation in vivo. To improve efficiency of delivery gene transfer to the vein grafts, 20% poloxamer F-127 gel was used to increase virus contact time and 0.25% trypsin to increase virus penetration. Morphometric analyses and cellular proliferation were assessed for neointimal hyperplasia and VSMC proliferation. Results: miR-21 sponge can significantly decrease the expression of miR-21 and proliferation in cultured VSMCs. Cellular proliferation rates were significantly reduced in miR-21 sponge-treated grafts compared with controls at 28 days after bypass surgery (14.6±9.4 vs 34.9±10.8%, P=0.0032). miR-21 sponge gene transfer therapy reduced the intimal/media area ratio in vein grafts compared with the controls (1.38±0.08 vs. 0.6±0.10, P<0.0001). miR-21 sponge treatment also improved vein graft hemodynamics. We further identified that phosphatase and tensin homolog (PTEN) is a potential target gene that was involved in the miR-21-mediated effect on neointimal hyperplasia in vein grafts. Conclusions: Adenovirus-mediated miR-21 sponge gene therapy effectively reduced neointimal formation in vein grafts. These results suggest that there is potential for miR-21 sponge to be used to prevent vein graft failure.

[Analysis of the risk factors of acute renal insufficiency following coronary artery bypass grafting].

OBJECTIVE: To study the risk factors of acute renal insufficiency (ARI) following coronary artery bypass grafting (CABG). METHODS: The clinic data of 2242 patients undertaking CABG between July 1997 and July 2006 were retrospectively analyzed, and ARI following CABG was included. RESULTS: ARI occurred in 219 patients, with an incidence of 9.8%. Univariate analysis revealed that advanced age, diabetes mellitus, preoperative chronic renal dysfunction, left main disease, low left ventricular erection faction, emergency operation, on-pump CABG, ascending aortic atherosclerosis, postoperative respiratory function insufficiency and low cardiac output syndrome were significantly related to ARI following CABG, and logistic multivariate regression analysis showed that presence of advanced age (P = 0.031), preoperatively chronic renal dysfunction (CrCl or= 150 micromol/L, P = 0.041), on-pump CABG (P < 0.001), postoperative respiratory function insufficiency (P = 0.013) and low cardiac output syndrome (P = 0.004) were independent risk factors of ARI. CONCLUSIONS: Advanced age, preoperatively chronic renal dysfunction, on-pump CABG, postoperative respiratory function insufficiency and low cardiac output syndrome are the risk factors of ARI following CABG.

Minimally invasive direct coronary bypass compared with percutaneous coronary intervention for left anterior descending artery disease: a meta-analysis.

BACKGROUND: The clinical outcomes for left anterior descending (LAD) coronary artery lesion between minimally invasive direct coronary artery bypass (MIDCAB) and percutaneous coronary intervention (PCI) are still controversial. The objective was to compare safety and efficacy between MIDCAB and PCI for LAD. METHODS: Electronic databases and article references were systematically searched to access relevant studies. End points included mortality, myocardial infarction, target vessel revascularization (TVR), major adverse coronary events (MACE), angina recurrence, and stroke. RESULTS: Fourteen studies with 941 patients were finally involved in the present study. The mortality and incidence of myocardial infarction were similar in MIDCAB and PCI groups at 30 days, 6 months, and at follow-up beyond 1 year. Compared with PCI, MIDCAB decreased incidence of TVR and MACE at 6 months and beyond 1 year follow-up. MIDCAB was associated with a lower incidence of angina recurrence at 6 months compared with PCI. PCI was associated with higher risk of restenosis in target vessel. No significant difference was shown for stroke. CONCLUSION: Our meta-analysis indicates that there are no significant differences in the safety between MIDCAB and PCI in patients with LAD. However MIDCAB is superior to PCI for TVR and MACE.

MicroRNA-221 sponge therapy attenuates neointimal hyperplasia and improves blood flows in vein grafts.

BACKGROUND: Vein graft failure due to neointimal hyperplasia remains an important and unresolved problem of cardiovascular surgery. MicroRNA-221 (miR-221) has been shown to play a major role in regulating vascular smooth muscle cell (VSMC) proliferation and phenotype transformation. Thus, the purpose of this study is to determine whether adenovirus mediated miR-221 sponge gene therapy could inhibit vein graft neointimal hyperplasia. METHODS: Adenovirus encoding miR-221 sponge (Ad-miR-221-SP) was used to inhibit VSMC proliferation in vitro and neointimal formation in vivo. Expression of miRNA-221 was evaluated in cultured VSMC and in rat vein graft models following transduction with Ad-miR-221-SP, Ad-Control-SP (without miR-221 antisense binding sites), or Ad-GFP (control). To accelerate the transfer of miR-221 sponge gene to the vein grafts, 20% poloxamer F-127 gel was used to extend virus contact time and 0.25% trypsin to increase virus penetration. RESULTS: miR-221 sponges can significantly decrease the expression of miR-221 and proliferation in cultured VSMC. Cellular proliferation rates were significantly reduced in miR-221 sponge treated grafts as compared with controls at 6 weeks after bypass surgery (19.8% versus 43.6%, P=0.0028). miR-221 sponge gene transfer reduced the neointimal area (210.75 ± 24.13 versus 67.01 ± 12.02, P<0.0001), neointimal thickness (171.86 ± 27.87 versus 64.13 ± 16.23, P<0.0001) and neointima/media ratio (0.74 ± 0.21 versus 1.95 ± 0.25, P<0.0001) in vein grafts versus controls. miR-21 sponge treatment was also improved hemodynamics in vein grafts. We have further identified that p27 (Kip1) is a potential target gene of miR-221 in vein grafts. CONCLUSION: miR-221 sponge therapy can significantly reduce miR-221 activity and inhibit neointimal hyperplasia in vein grafts. Locally adventitial delivery of adenoviruses mediated miRNA sponges may be promising gene therapies to prevent vein graft failure.