Long non-coding RNA XIST negatively regulates thoracic aortic aneurysm cell proliferation by targeting the miR-193a-5p/KLF7 axis.

Non-coding RNAs (ncRNAs) are important molecular modulators in diverse pathological processes, influencing the occurrence and progression of carcinomas. Thoracic aortic aneurysm (TAA) is an infrequent disease among aneurysmal diseases and accounts for nearly 3% of diagnosed aneurysms. The functional roles of long ncRNA (lncRNA) XIST and miR-193a-5p and the associated molecular mechanisms are yet to be investigated. In the current study, we discovered that miR-193a-5p was expressed at low levels in the blood of TAA patients. Further, loss-of-function and gain-of-function assays disclosed that miR-195-3p impacted the proliferation ability of TAA cells. XIST was found to be the most overexpressed lncRNA among predicted lncRNAs binding to miR-193a-5p. The promotive function of XIST in TAA was also explored. Subsequently, KLF7 was proved to be the downstream factor of the XIST/miR-193a-5p axis. Rescue assays testified the whole regulation mechanism of the XIST/miR-193a-5p/KLF7 axis in TAA. MiR-193a-5p was absorbed by XIST for the improvement of KLF7 in TAA. These results concluded that XIST might be engaged in TAA pathogenesis via regulation of the miR-193a-5p/KLF7 axis, supplementing more therapeutic options for TAA treatment.

Clinical Outcome of Reoperation for Mechanical Prosthesis at Aortic Position.

AIM: Redo aortic valve surgery is usually associated with a high risk of mortality and complications. The aim of this study was to investigate the perioperative and long-term outcomes of reoperation after prior mechanical prosthesis implantation at the aortic position. METHOD: The clinical data of 146 consecutive patients who underwent reoperation at the aortic position between 2003 and 2019 were analysed. RESULTS: Mean age was 51.5±12.7 years and 69 (47.3%) were female. The median interval from prior surgery to redo aortic valve surgery was 6 years. The aetiologies were pannus formation with prosthetic aortic stenosis in 62 cases (42.5%), prosthetic valve endocarditis (PVE) in five (3.4%), PVE with perivalvular leakage (PVL) in 16 (11.0%), PVL in 45 (30.8%), thrombosis in seven (4.8%), and aortic disease in 11 (7.5%). As for surgical procedure, aortic valve replacement was performed in 81 cases (55.5%), Bentall in 34 (23.3%), PVL repair in six (4.1%), and pannus debridement in 25 (17.1%). Fourteen (14) (9.6%) patients expired perioperatively. Prolonged ventilation time and postoperative renal failure were proved to be significant independent predictors of mortality according to multivariate analysis. Overall survival was 87.8%±7.4% and 76.4%±15.1% at 5 and 10 years, respectively. Survival was 87.7%±13.7% and 84.2%±15.6% in the pannus group, and 84.5%±12.6% and 74.6%±19.4% in the non-pannus group at 5 and 10 years, respectively (p=0.951). Survival was 87.5%±14.2% and 75.8%±22.7% in the PVL group and 84.7%±11.9% and 81.6%±13.5% in the non-PVL group at 5 and 10 years, respectively (p=0.365). CONCLUSIONS: Pannus formation and PVL are two major indications for reoperation of mechanical prosthesis at the aortic position. Redo aortic valve surgery has a satisfactory outcome but with a high risk of complications. Long-term survival of patients seems not to be related to the aetiology. Final decision-making of redo aortic valve surgery should be based on aetiology.

IgG4-Related Tumefactive Lesions at the Pulmonary Artery Causing Stenosis of Bilateral Primary Branches and Resultant Pulmonary Hypertension.

IgG4-related disease (IgG4-RD) is a newly recognized but rare entity involving multiple organs, with autoimmune pancreatitis, retroperitoneal mass, and the inflammation of glands being typical in most cases. IgG4-related perivascular lesions, although uncommon, have been increasingly reported in recent years. Diagnosis of IgG4-RD relies on comprehensive consideration of characteristic histopathological and immunostaining results, clinical and imaging findings, and serological results according to several widely recognized diagnostic criteria. This benign disorder frequently presenting tumefactive lesions should be distinguished from malignancy and other inflammatory mimics. Here we report a case of tumefactive mass at the bifurcation of the pulmonary trunk causing stenosis of the proximal left and right pulmonary artery (PA) and resultant pulmonary hypertension (PH). Bypass from the PA trunk to the right branch distal to stenosis was performed to resolve the obstructive hemodynamic disturbance and PH. Glucocorticoid monotherapy was performed after a diagnosis of definite IgG4-RD. Longitudinal disease activity assessment via imaging modalities, serological parameters, and IgG4-RD responder index verified no relapse during follow-up and the validity of the treatment strategy.

Retrograde Type A Dissection after Ascending Aorta Involved Endovascular Repair and Its Surgical Repair with Stented Elephant Trunk.

BACKGROUND: Retrograde type A dissection (RTAD) is a serious complication after ascending aorta involved endovascular repair (AAIER). We here report our surgical approach to this serious complication. METHODS: From July 2011 to July 2014, 8 RTADs after AAIER patients received surgical repair in our institution. Data of these RTAD patients were retrospectively collected for further analysis. All patients received urgent surgical repair based on the stented elephant trunk technique. We took 2 different ways to handle the previous stent during operation. In patients who had a prior hybrid aortic repair, we removed the proximal part of the stent while the distal part was left in place. In patients who had prior ascending aorta stent implantation (AASI), the stent was totally removed. RESULTS: The mean age of the patients was 57.6 ± 11.9 years. Regarding the index intervention, 2 patients received hybrid aortic repair and 6 patients received AASI. In patients who received AASI, 1 patient underwent simultaneous thoracic endovascular aortic repair (TEVAR) and another patient received simultaneous chimney technique in innominate artery and left common carotid artery combined with bypass from left subclavian artery to left common carotid artery to cure the type I endoleak induced by the previous implanted TEVAR stent. All patients received a new elephant trunk implantation during surgical repair. The mean cardiopulmonary bypass, selective cerebral perfusion, and aortic cross-clamp time were 172.1 ± 13.3, 40.8 ± 4.2, and 121.8 ± 11.4 min, respectively. The mean intensive care unit time was 7.8 ± 3.4 days. Two patients (25.0%) experienced transient neurologic dysfunction and recovered completely before discharge. In-hospital death rate was 12.5% (1 of 8). The mean follow-up time was 17.1 ± 9.5 months. No late deaths or complications occurred during follow-up. CONCLUSIONS: AAIER especially AASI used in aortic dissection treatment should be seriously considered since RTAD might occur. Our study indicated that surgical repair with stented elephant trunk was feasible and according to the cause of RTAD, different surgical strategies should be taken to manage the stent.

Response Gene to Complement-32 Promotes the Imbalance of Treg/Th17 in Patients with Dilated Cardiomyopathy.

BACKGROUND/AIMS: The imbalance of Treg/Th17 cells plays important role in the pathogenesis of dilated cardiomyopathy (DCM). Response gene to complement (RGC)-32 is a cell cycle regulator that plays an important role in cell proliferation. We evaluated whether the upregulation of RGC-32 was implicated in the homeostasis of Treg/Th17 cells in DCM. METHODS: The levels of plasma RGC-32, IL-17 and TGF-ß1, and the frequencies of circulating CD4+ RGC-32+ T cells, Th17 and Treg cells in patients with DCM were determined by Cytokine-specific sandwich ELISA and the flow cytometer (FCM), respectively. RESULTS: A significant elevation of plasma RGC-32 in patients with DCM compared with healthy control (HC) subjects was observed. This upregulation was associated with an increase in frequency of Th17 and a decrease in frequency of Treg cells. To further assessed the role of RGC-32, we investigated the effects of RGC-32 up- or down-regulation on frequencies of Th17 and Treg cells in peripheral blood mononuclear cells (PBMCs) from subjects. Importantly, overexpression of RGC-32 was accompanied by an augmentation of Th17 and a reduction of Treg expression. CONCLUSION: In summary, our study demonstrated the up-regulation of RGC-32 contributed to the imbalance of Treg/Th17 cells in patients with DCM.

Measurement of oxygen consumption in children undergoing cardiac catheterization: comparison between mass spectrometry and the breath-by-breath method.

Accurate measurement of oxygen consumption (VO2) is important to precise calculation of blood flow using the Fick equation. This study aimed to validate the breath-by-breath method (BBBM) of measuring oxygen consumption VO2 compared with respiratory mass spectroscopy (MS) for intubated children during cardiac catheterization. The study used MS and BBBM to measure VO2 continuously and simultaneously for 10 min in consecutive anesthetized children undergoing cardiac catheterization who were intubated with a cuffed endotracheal tube, ventilated mechanically, and hemodynamically stable, with normal body temperature. From 26 patients, 520 data points were obtained. The mean VO2 was 94.5 ml/min (95 % confidence interval [CI] 65.7-123.3 ml/min) as measured by MS and 91.4 ml/min (95 % CI 64.9-117.9 ml/min) as measured by BBBM. The mean difference in VO2 measurements between MS and BBBM (3.1 ml/min; 95 % CI -1.7 to +7.9 ml/min) was not significant (p = 0.19). The MS and BBBM VO2 measurements were highly correlated (R (2) = 0.98; P < 0.0001). Bland-Altman analysis showed good correspondence between MS and BBBM, with a mean difference of -3.01 and 95 % limits of agreement ranging from -26.2 to +20.0. The mean VO2 indexed to body surface area did not differ significantly between MS and BBBM (3.4 ml/min m(2); 95 % CI -1.4 to 8.2; p = 0.162). The mean difference and limits of agreement were -3.8 ml/min m(2) (range, -19.9 to 26.7). Both MS and BBBM may be used to measure VO2 in anesthetized intubated children undergoing cardiac catheterization. The two methods demonstrated excellent agreement. However, BBBM may be more suited to clinical use with children.

Ni-catalysed assembly of axially chiral alkenes from alkynyl tetracoordinate borons via 1,3-metallate shift.

Asymmetric synthesis based on a metallate shift of tetracoordinate borons is an intriguing and challenging topic. Despite the construction of central chirality from tetracoordinate boron species via a 1,2-metallate shift, catalytic asymmetric synthesis of axially chiral compounds from such boron 'ate' complexes is an ongoing challenge. Axially chiral alkenes have received great attention due to their unique characteristics and intriguing molecular scaffolds. Here we report an enantioselective nickel-catalysed strategy for the construction of axially chiral alkenes via a 1,3-metallate shift of alkynyl tetracoordinate boron species. The chemoselectivity, regioselectivity and atroposelectivity can be regulated and well-controlled from readily accessible starting materials with a cheap transition-metal catalyst. Downstream transformations indicate the powerful conversion ability of such compounds in this protocol, and late-stage elaborations of bioactive compounds can also be achieved. Mechanistic experiments reveal that regioselective syn-addition of an aryl-Ni complex with a carbon-carbon triple bond and subsequent 1,3-phenyl migration are the two key steps for the synthesis of axially chiral alkenes.

Characteristics of pericardial interstitial cells and their implications in pericardial fibrocalcification.

Pericardial fibrocalcification (PF) is a prominent feature of human pericardial pathology, including constrictive pericarditis and, to a lesser extent, degenerated autologous pericardial substitutes. However, the role of pericardial interstitial cells (PICs) in the pathogenesis of PF has yet to be established. Using a combination of histology and immunohistochemistry, we showed that the critical cellular event in PF in situ was the transdifferentiation of PICs into myofibroblasts/osteoblasts and that the percentage of myofibroblasts/osteoblasts correlated positively with the severity of PF. In vitro studies demonstrated that PICs, similar to mesenchymal stem cells, had the potential to differentiate along adipogenic, osteogenic, chondrogenic or myogenic lineages. However, PICs exhibited a more limited self-renewal capacity and a lower expression of Oct4 (POU5F1) and Kruppel-like transcription factor Klf4, underwent earlier senescence and spontaneously transdifferentiated into myofibroblasts/osteoblasts. Quantitative-real-time reverse transcriptase-polymerase chain reaction (qRT-PCR) confirmed that the mRNA levels of α-smooth muscle actin (α-SMA), alkaline phosphatase (ALP), core-binding factor α1/runt-related transcription factor2 (Cbfa1/Runx2), transforming growth factor (TGF)-ß1 and bone morphogenetic protein (BMP)-2 were upregulated as the passage number increased. The mRNA level of platelet-derived growth factor (PDGF)-AA was also significantly upregulated with higher levels at passage 3. Ectopic expression of Oct4 and Klf4 enhanced the colony formation of PICs and selectively impaired induction of genes involved in transdifferentiation into myofibroblasts/osteoblasts (α-SMA, ALP, Cbfa1/Runx2, PDGF-AA and BMP-2). These data, while offering new insights into the biology of PICs, reinforce the central role of these cells in cell-mediated PF and may assist in future strategies to treat fibrocalcific pericardial diseases.

Surgical Outcomes of Stent-Related Type A Dissection Compared with Spontaneous Type A Dissection.

OBJECTIVE: Aortic endovascular stent implantation includes thoracic endovascular aortic repair (TEVAR), hybrid aortic repair (HAR), and ascending aorta stent implantation (AASI). In this study, we compared the surgical outcomes of stent-related type A dissection (SRTAD) compared with spontaneous type A dissection (STAD). METHODS: From July 2011 to July 2014, we identified 17 SRTAD patients received surgical repair in our institution. Propensity score-matching was used to identify 34 STAD patients as controls. RESULTS: Preoperative data of SRTAD group and STAD group had no statistical difference. Selective cerebral perfusion (SCP) time was longer in SRTAD group than in STAD group (P <0.05). SRTAD group had a longer cross-clamp time compared with STAD group (P <0.05). No intraoperative deaths in two groups. No differences in CPB time and concomitant procedures between two groups. In-hospital mortality was 11.76% (2 of 17) in SRTAD group and 2.9% (1 of 34) in STAD group (P <0.05). No differences were found in intensive care unit (ICU) time, ventilation, paraparesis, and other postoperative complications between SRTAD and STAD groups. No difference was found in survival rate between SRTAD and STAD groups in the postoperative 1-year follow-up. CONCLUSIONS: SRTAD patients received surgical repair had a higher in-hospital mortality compared with STAD, but no differences were found in postoperative complications and mid-term outcomes.

Impact of prosthesis-patient mismatch on early and late outcomes after mitral valve replacement: a meta-analysis.

BACKGROUND: Prognostic significance of prosthesis-patient mismatch (PPM) after mitral valve replacement (MVR) remains uncertain because of the limited studies reporting inconsistent or even contrary results. This meta-analysis pooled results of all available studies comparing early and late prognoses between patients with significant mitral PPM and those without. METHODS: Studies were identified by searching Pubmed, Excerpta Medica Database, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov. Impact of PPM on postoperative hemodynamic results, thirty-day mortality, overall mortality, mortality of thirty-day survivors, and primary morbidity after MVR was evaluated via meta-analysis. Robustness of pooled estimates, source of heterogeneity, and publication bias were assessed via sensitivity analyses, meta-regression as well as subgroup analysis stratified according to methodological or clinical heterogeneity, or sequential omission method, and funnel plot or Begg's and Egger's tests, respectively. RESULTS: Nineteen cohort studies involving 9302 individuals (PPM group: n = 5109, Control group: n = 4193) were included for meta-analysis. Total PPM and severe PPM prevalence were 3.8%-85.9% and 1%-27%, with a mean value of 54.9% and 14.1%, respectively. As compared with control group, mitral PPM group demonstrated a poorer postoperative hemodynamic status of higher mean and peak residual transprosthetic pressure gradients (TPG), higher postoperative systolic pulmonary artery pressure (SPAP) and less reduction, higher postoperative pulmonary hypertension (PH) prevalence and less PH regression, smaller net atrioventricular compliance, less NYHA class decrease, higher postoperative functional tricuspid regurgitation prevalence and less regression. The PPM group also revealed a higher thirty-day mortality, long-term overall mortality, mortality of thirty-day survivors, and postoperative congestive heart failure prevalence, which were positively correlated with the severity of PPM if it was classified into tri-level subgroups. Left ventricular end-diastolic diameter, postoperative atrial fibrillation (AF) prevalence, and the AF regression were analogous between groups. Most pooled estimates were robust according to sensitivity analyses. Male patients and bioprosthesis implantation proportion were prominent source of between-study heterogeneity on thirty-day mortality. Publication bias was not significant in tests for all the outcomes, except for SPAP and TPG. CONCLUSIONS: Mitral PPM would result in poorer postoperative hemodynamics and worse early and late prognosis. Severe PPM must be avoided since deleterious impact of mitral PPM was severity dependent.

miR-214 Attenuates Aortic Valve Calcification by Regulating Osteogenic Differentiation of Valvular Interstitial Cells.

Calcific aortic valve disease (CAVD) is a common heart valve disease in aging populations, and aberrant osteogenic differentiation of valvular interstitial cells (VICs) plays a critical role in the pathogenesis of ectopic ossification of the aortic valve. miR-214 has been validated to be involved in the osteogenesis process. Here, we aim to investigate the role and mechanism of miR-214 in CAVD progression. miR-214 expression was significantly downregulated in CAVD aortic valve leaflets, accompanied by upregulation of osteogenic markers. Overexpression of miR-214 suppressed osteogenic differentiation of VICs, while silencing the expression of miR-214 promoted this function. miR-214 directly targeted ATF4 and Sp7 to modulate osteoblastic differentiation of VICs, which was proved by dual luciferase reporter assay and rescue experiment. miR-214 knockout rats exhibited higher mean transvalvular velocity and gradient. The expression of osteogenic markers in aortic valve leaflets of miR-214 knockout rats was upregulated compared to that of the wild-type group. Taken together, our study showed that miR-214 inhibited aortic valve calcification via regulating osteogenic differentiation of VICs by directly targeting ATF4 and Sp7, indicating that miR-214 may act as a profound candidate of targeting therapy for CAVD.

Long-term outcomes of surgical procedures for Marfan syndrome: aortic dissection versus aneurysm.

BACKGROUND: Multiple of subsequent procedures may necessary in Marfan syndrome (MFS) patients after initial surgery. The aim of this study was to investigate the full spectrum of secondary distal vascular or valvular interventions encountered after initial surgery. METHODS: Retrospective analysis of 201 consecutive MFS patients between January 2000 and March 2019 who underwent 274 distal aortic reinterventions and 5 mitral valve replacements. RESULTS: Of the enrolled 201 MFS patients (73 female, mean age 37.0±12.8 years), the surgical indication for 93 patients was aortic root aneurysm, and for another 108 patients was dissection. The mean follow-up interval was 8.4±5.5 years. Total arch replacement (TAR) was performed in 68.5% of MFS patients presenting with type A aortic dissection (TAAD) and in 2.2% of patients with aneurysm. Secondary TAR became necessary for 3.4% of patients who failed to receive TAR at initial surgery in aneurysm group during follow-up, while for 33.3% of patients in dissection group (P<0.001). Freedom from distal aortic reoperation in dissection group were 65.4%±5.2%, 49.6%±6.4%, and 38.3%±7.7% and in aneurysm group were 90.5%±3.5%, 84.2%±4.8%, and 84.2%±4.8% at 5, 10, and 15 years, respectively (P<0.001). Survival in dissection group were 94.4%±2.4%, 83.4%±5.7%, 68.4%±10.8% and in aneurysm group were 100%, 97.7%±2.3%, 97.7%±2.3% at 5, 10, and 15 years, respectively (P=0.001). Freedom from mitral valve reoperation in dissection group were 98.8%±1.2%, 98.8%±1.2%, 88.9%±9.4% at 5, 10, and 15 years, respectively. Freedom from mitral valve reoperation in aneurysm group were 97.2%±1.9%, 94.6%±3.2%, 94.6%±3.2% at 5, 10, and 15 years, respectively (P=0.775). CONCLUSIONS: TAAD at initial surgery was an independent predictor of distal aortic reoperation. Limited repair was feasible for MFS patients presenting with aneurysm at initial surgery, extended repair might be better for TAAD for its higher risk of distal reintervention. Concomitant mitral valve procedures may depend on mitral regurgitation grades.

[Recombinant adeno-associated virus mediated RNA interference of angiogenin expression inhibits cell growth of human lung adenocarcinoma].

OBJECTIVE: To study the inhibition of angiogenin (ANG) expression in human lung squamous cancer cell strain-A549 through adeno-associated virus (AAV)-mediated RNA-interference, and therefore to observe its effect on the growth of cancer cells and tumor formation. METHODS: Recombinant AAV expressing H1-promoter-induced small-interference- RNA (siRNA) targeting ANG (AAV-shANG) was constructed, and then transfected into A549 cells. A549 cells and cells transfected with AAV-Null were used as the control groups. The effects of the reduced expression of ANG by RNAi from AAV-shANG on the growth, formation, reproduction, apoptosis, and microvessel-density of the carcinoma were observed. RESULTS: In vitro experiment showed that AAV-shANG was constructed successfully, There was an significant decrease in the expression of ANG protein 72 h after transfection, compared with the normal A459 cells and AAV-Null cells (P < 0.01). Cell cycle analysis showed that the proliferation index (PI) of normal A549 cells, AAV-Null cells and AAVshANG cells were 0.32 +/- 0.29, 0.35 +/- 0.38 and 0.31 +/- 0.43, respectively. There was no statistic difference in the PIs among the 3 groups (P > 0.05). In vivo experiment using thymus-defect mice showed that, there was an remarkable reduction in the mass and volume of tumors in AAV-shANG transfected group, compared to the control groups. Microvessel-density was 9.4 +/- 1.5, 9.8 +/- 2.1 and 5.7 +/- 1.9, respectively in the 3 groups, a statistic difference among the AAV-shANG-transfected group, the normal A549 group and the AAV-Null transfected group. The percentages of apoptotic cells in each group were (7.7 +/- 3.1)%, (8.5 +/- 5.4)%, (17.1 +/- 8.6)%, respectively, the experimental group being higher than those of the control groups. Positive rates of PCNA were (84.8 +/- 9.7)%, (85.8 +/- 9.8)%, and (70.4 +/- 10.1)%, respectively, the AAV-shANG transfected cancer cells showing a lower PCNA index than the control groups. CONCLUSION: AAV-mediated expression of siRNA could reduce the expression of ANG in cancer cells, significantly enough to inhibit cell proliferation, promote cell apoptosis and inhibit tumor growth.

Hybrid Reconstruction of the Aortic Arch Using a Double-Branched Stent-Graft in a Canine Model.

Purpose: To report the results of a hybrid approach to aortic arch repair using an innovative unibody double-branched stent graft in a canine model.Materials and methods: The stent-graft system consists of two parts: the main body and two branches for reconstruction of the supra-arch branches. There is a 2-cm-long suturing portion at the proximal end of the main body. Twenty adult German sheep dogs underwent a hybrid surgical treatment to place the stent-grafts into the proximal descending aorta and the supra-arch branches. Outcomes were assessed by operative mortality, complications, imaging studies, and histomorphometric analyses.Results: Placement of the stent-graft was performed successfully in all dogs without complications. One dog died of respiratory failure due to early extubation. The other dogs survived to 6 months without complications, at which time they were sacrificed. The mean cardiopulmonary bypass time was 80.3 ± 7.3 mins and hypothermic circulatory arrest time was 10.7 ± 1.9 min. The average blood loss was 373.5 mL. At 6 months, postoperative aortic imaging indicated that the main body and branches of the stent-graft were fully open and in satisfactory position. No migration, deformation, or endovascular leakage was observed. Histomorphometric results showed normal arrangement of medial and adventitial elastic fibers, moderately proliferated intima, with or without neo-microvessels, and microscopic morphological changes in internal elastic lamina.Conclusions: These results demonstrate that it is possible and safe to reconstruct the aortic arch with the novel open-branched stent-graft placement.

Involvement of Oct4 in the pathogenesis of thoracic aortic dissection via inducing the dedifferentiated phenotype of human aortic smooth muscle cells by directly upregulating KLF5.

OBJECTIVE: To investigate the expression of Oct4 in human thoracic aortic dissection (TAD) and the regulation mechanisms of Oct4 on phenotype transition of human aortic smooth muscle cells (HASMCs). METHODS: Aortic samples from TAD patients (n = 12) and organ donors (n = 6) were collected. qRT-PCR, western blot, and immunohistochemistry were performed to identify Oct4 expression in aortic media. Immunofluorescence was performed to analyze Oct4 expression in primary HASMCs. Oct4A and Oct4B isoforms were detected. Gain-of-function experiments were performed to determine the effects of Oct4 on HASMC phenotype transition. Chromatin immunoprecipitation, luciferase assay, and rescue experiments were performed to analyze mechanisms of Oct4 on HASMC phenotype transition. RESULTS: Oct4 expression levels, especially the Oct4A isoform, were significantly higher in TAD patients compared with normal controls. Notably, Oct4 presented a strong and strict nuclear localization in primary HASMCs of TAD patients but a mild and diffuse distribution in both cytoplasm and nucleus in the control group. Overexpression of Oct4 induced dedifferentiation of HASMCs characterized by decreased contractile proteins and elevated migration capability. Krüppel-like factor 5 (KLF5) was found to be a directly regulated target gene of Oct4 in HASMCs. Furthermore, downregulation of KLF5 significantly alleviated the effects of Oct4 on phenotype transition of HASMCs. CONCLUSIONS: Oct4 expression was significantly upregulated in aortic tissues and primary HASMCs of TAD patients. The increased Oct4 induced phenotype transition of HASMCs from the contractile type to the synthetic type by directly upregulating KLF5.

Consumption of whole grains in relation to mortality from all causes, cardiovascular disease, and diabetes: Dose-response meta-analysis of prospective cohort studies.

BACKGROUND: To investigate the correlation between consumption of whole grains and the risk of all-cause, cardiovascular disease (CVD), and diabetes-specific mortality according to a dose-response meta-analysis of prospective cohort studies. METHODS: Observational cohort studies, which reported associations between whole grains and the risk of death outcomes, were identified by searching articles in the MEDLINE, EMBASE, and the reference lists of relevant articles. The search was up to November 30, 2015. Data extraction was performed by 2 independent investigators, and a consensus was reached with involvement of a third. RESULTS: Ten prospective cohort studies (9 publications) were eligible in this meta-analysis. During follow-up periods ranging from 5.5 to 26 years, there were 92,647 deaths among 782,751 participants. Overall, a diet containing greater amounts of whole grains may be associated with a lower risk of all-cause, CVD-, and coronary heart disease (CHD)-specific mortality. The summary relative risks (RRs) were 0.93 (95% confidence intervals [CIs]: 0.91-0.95; Pheterogeneity < 0.001) for all-cause mortality, 0.95 (95% CIs: 0.92-0.98; Pheterogeneity < 0.001) for CVD-specific mortality, and 0.92 (95% CIs: 0.88-0.97; Pheterogeneity < 0.001) for CHD-specific mortality for an increment of 1 serving (30 g) a day of whole grain intake. The combined estimates were robust across subgroup and sensitivity analyses. Higher consumption of whole grains was not appreciably associated with risk of mortality from stroke and diabetes. CONCLUSION: Evidence from observational cohort studies indicates inverse associations of intake of whole grains with risk of mortality from all-cause, CVD, and CHD. However, no associations with risk of deaths from stroke and diabetes were observed.

Proximal aortic repair versus extensive aortic repair in the treatment of acute type A aortic dissection: a meta-analysis.

OBJECTIVES: The optimal surgical strategy for acute type A aortic dissection (ATAAD) is still controversial because of the inconsistent or even conflicting results of proximal aortic repair (PR) versus extensive aortic repair (ER) on early and late prognostic outcomes. This meta-analysis pooled data from all available studies of PR versus ER to get a summarized conclusion. METHODS: Studies were identified by searching the Medline, EMBASE and Cochrane databases. Early and late prognostic outcomes of interest were evaluated with meta-analysis. Fixed- or random-effect models were used according to the significance of heterogeneity. Robustness of pooled estimates and the source of heterogeneity were assessed via sensitivity analyses and meta-regression, respectively. Publication bias was evaluated by the funnel plot and Egger's test. RESULTS: Nine studies with a total of 1872 patients were included for the meta-analysis. Pooled results indicated that, when compared with the ER procedure, PR was associated with lower early mortality [risk ratio (RR) = 0.69, 95% confidence interval (CI) 0.54-0.90, P = 0.005] but higher incidence of postoperative aortic events including reoperation of the distal aorta (RR = 3.14, 95% CI 1.74-5.67, P < 0.001). PR and ER demonstrated analogous prognosis on long-term mortality (HR = 1.02, 95% CI 0.51-2.06, P = 0.96) and the incidences of early postoperative renal failure (RR = 0.75, 95% CI 0.49-1.14, P = 0.17) and stroke (RR = 0.73, 95% CI 0.30-1.78, P = 0.50). All the pooled results were robust to sensitivity analysis. Heterogeneity was insignificant except for the meta-analysis of late mortality. CONCLUSIONS: Performing a less aggressive initial surgical procedure of PR in ATAAD patients would have lower early mortality but elevated incidence rates of late aortic reintervention, when compared with ER. Other prognostic results of the two surgical strategies including long-term mortality were similar for both.

Brahma-related gene 1 inhibits proliferation and migration of human aortic smooth muscle cells by directly up-regulating Ras-related associated with diabetes in the pathophysiologic processes of aortic dissection.

OBJECTIVE: To elucidate the mechanisms of Brahma-related gene 1 (Brg1) involvement in the pathophysiologic processes of aortic dissection. METHODS: Seventeen dissecting, 4 dilated, and 10 healthy human aorta samples were collected. Expression of Brg1 in the medium of aorta was evaluated by quantitative real-time polymerase chain reaction, Western blot, and immunohistochemical staining, respectively. The regulation effect of Brg1 on proliferation and migration of human aortic smooth muscle cells (HASMCs) was analyzed in 3 ways: using cell counting, a migration chamber, and a wound scratch assay. A polymerase chain reaction array was used for screening potential target genes of Brg1. A chromatin immunoprecipitation assay was adopted for direct deoxyribonucleic acid-protein binding detection. RESULTS: Expression levels of Brg1 were increased in aortic dissection and aortic dilation patients. In vitro results indicated that overexpression of Brg1 inhibited proliferation and migration of HASMCs. The candidate proliferation- and migration-related Brg1 target gene found was Ras-related associated with diabetes (RRAD), expression levels of which were enhanced in dissecting aortic specimens. The direct regulation effect of Brg1 on RRAD was verified by chromatin immunoprecipitation assay results. Furthermore, down-regulating RRAD significantly alleviated the suppression effects of Brg1 on proliferation and migration of HASMCs. CONCLUSIONS: Our study illustrated that Brg1 inhibited the proliferation and migration capacity of HASMCs, via the mechanism of direct up-regulation of RRAD, thus playing an important role in the pathophysiologic processes of aortic dissection.

BRG1 expression is increased in thoracic aortic aneurysms and regulates proliferation and apoptosis of vascular smooth muscle cells through the long non-coding RNA HIF1A-AS1 in vitro.

OBJECTIVES: Brahma-related gene 1 (BRG1) and long non-coding RNAs (lncRNAs) play important roles in cellular processes. However, little is known regarding their roles in thoracic aortic aneurysms. We investigated BRG1 expression in thoracic aortic aneurysms and the roles of BRG1 and the lncRNA HIF 1 alpha-antisense RNA 1 in regulating the proliferation and apoptosis of aortic smooth muscle cells in vitro. METHODS: BRG1 mRNA and protein expression in human aortic media specimens were examined by quantitative real-time polymerase chain reaction, immunohistochemical staining and western blot. BRG1 expression was up-regulated by lentiviral vectors. Vascular smooth muscle cell proliferation and apoptosis were studied using Cell Counting Kit-8 and terminal deoxynucleotidyl transferase dUTP nick-end labelling assays. We performed western blots to detect Caspase3 and Bcl2 protein expression. LncRNAs regulated by BRG1 were identified through microarray in BRG1 gain- and loss-of-function vascular smooth muscle cells. Finally, the expression of HIF 1 alpha-antisense RNA 1 was reduced by siRNA and cell proliferation and apoptosis was studied using Cell Counting Kit-8 assays, caspase-3 activity assays and western blot. RESULTS: BRG1 expression in the aortic media was significantly higher in thoracic aortic aneurysms than in normal controls. Overexpression of BRG1 in human aortic smooth muscle cells promoted apoptosis and reduced proliferation. The expression of HIF 1 alpha-antisense RNA 1 was significantly down- and up-regulated in BRG1 knock-down and overexpressing vascular smooth muscle cells, respectively. We further demonstrated that suppression of HIF 1 alpha-antisense RNA 1 by siRNA in vascular smooth muscle cells reduced apoptosis and promoted proliferation. CONCLUSIONS: BRG1 is overexpressed in the aortic media of thoracic aortic aneurysms and the interaction between BRG1 and HIF 1 alpha-antisense RNA 1 plays a key role in the proliferation and apoptosis of vascular smooth muscle cells in vitro, which may contribute to the pathogenesis of thoracic aortic aneurysms.

Society of Thoracic Surgeons 2008 cardiac risk models predict in-hospital mortality of heart valve surgery in a Chinese population: a multicenter study.

OBJECTIVES: The Society of Thoracic Surgeons 2008 cardiac surgery risk models have been developed for heart valve surgery with and without coronary artery bypass grafting. The aim of our study was to evaluate the performance of Society of Thoracic Surgeons 2008 cardiac risk models in Chinese patients undergoing single valve surgery and the predicted mortality rates of those undergoing multiple valve surgery derived from the Society of Thoracic Surgeons 2008 risk models. METHODS: A total of 12,170 patients underwent heart valve surgery from January 2008 to December 2011. Combined congenital heart surgery and aortal surgery cases were excluded. A relatively small number of valve surgery combinations were excluded. The final research population included the following isolated heart valve surgery types: aortic valve replacement, mitral valve replacement, and mitral valve repair. The following combined valve surgery types were included: mitral valve replacement plus tricuspid valve repair, mitral valve replacement plus aortic valve replacement, and mitral valve replacement plus aortic valve replacement and tricuspid valve repair. Evaluation was performed by using the Hosmer-Lemeshow test and C-statistics. RESULTS: Data from 9846 patients were analyzed. The Society of Thoracic Surgeons 2008 cardiac risk models showed reasonable discrimination and poor calibration (C-statistic, 0.712; P = .00006 in Hosmer-Lemeshow test). Society of Thoracic Surgeons 2008 models had better discrimination (C-statistic, 0.734) and calibration (P = .5805) in patients undergoing isolated valve surgery than in patients undergoing multiple valve surgery (C-statistic, 0.694; P = .00002 in Hosmer-Lemeshow test). Estimates derived from the Society of Thoracic Surgeons 2008 models exceeded the mortality rates of multiple valve surgery (observed/expected ratios of 1.44 for multiple valve surgery and 1.17 for single valve surgery). CONCLUSIONS: The Society of Thoracic Surgeons 2008 cardiac surgery risk models performed well when predicting the mortality for Chinese patients undergoing valve surgery. The Society of Thoracic Surgeons 2008 models were suitable for single valve surgery in a Chinese population; estimates of mortality for multiple valve surgery derived from the Society of Thoracic Surgeons 2008 models were less accurate.