S-nitrosylation of AMPKγ impairs coronary collateral circulation and disrupts VSMC reprogramming.

Collateral circulation is essential for blood resupply to the ischemic heart, which is dictated by the contractile phenotypic restoration of vascular smooth muscle cells (VSMC). Here we investigate whether S-nitrosylation of AMP-activated protein kinase (AMPK), a key regulator of the VSMC phenotype, impairs collateral circulation. In rats with collateral growth and development, nitroglycerin decreases coronary collateral blood flow (CCBF), inhibits vascular contractile phenotypic restoration, and increases myocardial infarct size, accompanied by reduced AMPK activity in the collateral zone. Nitric oxide (NO) S-nitrosylates human recombinant AMPKγ1 at cysteine 131 and decreases AMP sensitivity of AMPK. In VSMCs, exogenous expression of S-nitrosylation-resistant AMPKγ1 or deficient NO synthase (iNOS) prevents the disruption of VSMC reprogramming. Finally, hyperhomocysteinemia or hyperglycemia increases AMPKγ1 S-nitrosylation, prevents vascular contractile phenotypic restoration, reduces CCBF, and increases the infarct size of the heart in Apoe-/- mice, all of which is rescued in Apoe-/-/iNOSsm-/- mice or Apoe-/- mice with enforced expression of the AMPKγ1-C130A mutant following RI/MI. We conclude that nitrosative stress disrupts coronary collateral circulation during hyperhomocysteinemia or hyperglycemia through AMPK S-nitrosylation.

Continuous Electrochemical Synthesis of Iso-Coumarin Derivatives from o-(1-Alkynyl) Benzoates under Metal- and Oxidant-Free.

A non-oxidant and metal-free strategy for synthesizing iso-coumarin by using a continuous electrochemical microreactor to initiate an oxidative cyclization reaction of o-(1-alkynyl) benzoate and radicals. This efficient and clean continuous electrosynthesis method not only avoids the complicated gas protection operation and production of by-products in the batch processes, but also help to overcome the difficulty that batch metal catalysis and electrocatalysis are difficult to scale up, and has the potential for pilot-scale experiment.

Non-Traumatic Splenic Rupture After Open Surgery for Type A Aortic Dissection: A Case Report and Literature Review.

Aortic dissection is a severe condition that involves a tear in the wall of the major artery carrying blood out of the heart (aorta). This cardiac disease has a high mortality, particularly Stanford type A, which involves the first part of the aorta. Aortic dissection is characterized by urgent onset, rapid progress, and poor outcome [Nienaber 2003; Mehta 2002]. Surgery is the most effective treatment. Although there have been remarkable recent advances in the understanding and management of various aspects of these complex surgeries, many potential complications remain. Non-traumatic splenic rupture is a rare postoperative complication of type A aortic dissection, and there are only a few published reports discussing this complication. Splenic rupture is a life-threatening cause of intraperitoneal bleeding and often is associated with the preexisting pathology of the spleen in the absence of trauma [Renzulli 2009]. Its manifestation is characterized by abdominal pain, left shoulder pain, and even shock. Because of the history of aortic dissection, physicians initially may suspect arterial rupture. In our report, we aim to present the possibility of splenic rupture as a complication of aortic dissection surgery and the need for immediate surgical intervention.

Effect of different types of cerebral perfusion for acute type A aortic dissection undergoing aortic arch procedure, unilateral versus bilateral.

BACKGROUND: Antegrade cerebral perfusion (ACP), including unilateral and bilateral, is most commonly used for cerebral protection in aortic surgery. There is still no consensus on the superiority of the two methods. Our research aimed to investigate the clinical effects of u-ACP and b-ACP. METHODS: 321 of 356 patients with type A aortic dissection were studied retrospectively. 124 patients (38.6%) received u-ACP, and 197 patients (61.4%) received b-ACP. We compared the incidence of postoperative neurological complications and other collected data between two groups. Besides, we also analyzed perioperative variables to find the potential associated factors for neurological dysfunction (ND). RESULTS: For u-ACP group, 54 patients (43.5%) had postoperative neurological complications, including 22 patients (17.7%) with permanent neurologic dysfunction (PND) and 32 patients (25.8%) with temporary neurologic dysfunction (TND). For b-ACP group, 47 patients (23.8%) experienced postoperative neurological complications, including 16 patients (8.1%) of PND and 31 patients (15.7%) of TND. The incidence of PND and TND were significantly different between two groups along with shorter CPB time (p = 0.016), higher nasopharyngeal temperature (p≦0.000), shorter ventilation time (p = 0.018), and lower incidence of hypoxia (p = 0.022). Furthermore, multivariate stepwise logistic regression analysis confirmed that preoperative neurological dysfunction (OR = 1.20, p = 0.028), CPB duration (OR = 3.21, p = 0.002), and type of cerebral perfusion (OR = 1.48, p = 0.017) were strongly associated with postoperative ND. CONCLUSIONS: In our study, it was observed that b-ACP procedure exhibited shorter CPB time, milder hypothermia, shorter ventilation time, lower incidence of postoperative hypoxia, and neurological dysfunction compared to u-ACP. Meanwhile, the incidence of ND was independently associated with three factors: preoperative neurological dysfunction, CPB time, and type of cerebral perfusion.

Incidence and Risk Factors of Delirium in Patients After Type-A Aortic Dissection Surgery.

OBJECTIVE: To study the incidence and related risk factors for postoperative delirium after type-A aortic dissection in patients who underwent Sun's procedure (total arch replacement using a tetrafurcate graft with stented elephant trunk implantation). DESIGN: A retrospective study. SETTING: A cardiac surgical intensive care unit. PARTICIPANTS: The study comprised 100 patients admitted to the intensive care unit for type-A aortic dissection. INTERVENTIONS: All patients underwent Sun's procedure with uniform preoperative and anesthetic treatment. MEASUREMENTS AND MAIN RESULTS: Delirium was evaluated using the Confusion Assessment Method for the intensive care unit. Baseline demographics and preoperative, intraoperative, and postoperative data were recorded and analyzed retrospectively via univariate analysis and multivariate logistic regression. The incidence of postoperative delirium was 34%, according to Confusion Assessment Method for the intensive care unit criteria. Univariate analysis revealed that 17 variables differed significantly among patients with and without delirium. Additional multivariate stepwise logistic regression analysis confirmed that cerebrovascular disease history, surgery duration, cardiopulmonary bypass duration, intubation time, and hypoxia were strongly associated with postoperative delirium. CONCLUSIONS: Delirium is a common postoperative complication of aortic dissection. Cerebrovascular disease history, surgery and cardiopulmonary bypass duration, postoperative hypoxia, and intubation time are independently associated with the development of delirium. Early diagnosis of delirium and modifying these factors properly may be helpful to improve patients' prognosis.

Simvastatin improves the homing of BMSCs via the PI3K/AKT/miR-9 pathway.

Bone marrow-derived mesenchymal stem cells (BMSCs) have great therapeutic potential for many diseases. However, the homing of BMSCs to injury sites remains a difficult problem. Recent evidence indicates that simvastatin stimulates AKT phosphorylation, and p-AKT affects the expression of chemokine (CXC motif) receptor-4 (CXCR4). Therefore, simvastatin may improve the expression of CXCR4 in BMSCs, and microRNAs (miRs) may participate in this process. In this study, we demonstrated that simvastatin increased both the total and the surface expression of CXCR4 in BMSCs. Stromal cell-derived factor-1α (SDF-1α)-induced migration of BMSCs was also enhanced by simvastatin, and this action was inhibited by AMD 3100(a chemokine receptor antagonist for CXCR4). The PI3K/AKT pathway was activated by simvastatin in this process, and LY294002 reversed the overexpression of CXCR4 caused by simvastatin. MiR-9 directly targeted CXCR4 in rat BMSCs, and simvastatin decreased miR-9 expression. P-AKT affected the expression of miR-9; as the phosphorylation of AKT increased, miR-9 expression decreased. In addition, LY294002 increased miR-9 expression. Taken together, our results indicated that simvastatin improved the migration of BMSCs via the PI3K/AKT pathway. MiR-9 also participated in this process, and the phosphorylation of AKT affected miR-9 expression, suggesting that simvastatin might have beneficial effects in stem cell therapy.

Effects of Ulinastatin on Perioperative Inflammatory Response and Pulmonary Function in Cardiopulmonary Bypass Patients.

The aim of this study was to investigate whether ulinastatin (UTL) has protective effects on perioperative proinflammatory cytokines and lung injury in cardiopulmonary bypass (CPB) patients. The study included 60 patients undergoing CPB who were randomly divided into a UTL group and a control group. Blood routine examination and inflammatory cytokines concentrations were detected after anesthetic induction (T1), immediately after aortic valve opening (T2), and 4 (T3) and 24 (T4) hours after weaning from CPB. Flow cytometry was used to detect TLR4 and HSP70 expressions. Arterial blood gas and respiratory function were analyzed at the same time points. Compared with the control group, the levels of IL-2, IL-8, TNF-α, NE, TLR4, PA - aDO2, and RI at T2 were significantly lower, whereas HSP70, PaO2, OI, Cd, and Cs were higher in the UTL group (all P < 0.05). Relative to the control group at T3, white blood cell count, TLR4, IL-2, IL-6, IL-8, TNF-α, NE, and RI decreased significantly, whereas IL-10, HSP70, PaO2, OI, and Cs increased in the UTL group (all P < 0.05). At T4, IL-2, IL-6, IL-8, TNF-α, TLR4, and PaCO2 in the UTL group were significantly lower, and PaO2, IL-10, HSP70, and Cs were higher than in the control group (all P < 0.05). Our data show strong evidence that UTL suppresses proinflammatory cytokine elevation and upregulates release of anti-inflammatory mediators, reducing pulmonary injury and improving pulmonary function after CPB.

Astrocyte-elevated gene-1 mediates insulin-like growth factor 1-induced the progression of cardiac myxoma.

Recently, astrocyte-elevated gene-1 (AEG-1) and insulin-like growth factor 1 (IGF-1) have been involved in the regulation of multiple signaling pathways in tumorigenesis. To date, the detailed mechanisms underlying IGF-1-AEG-1 pathway-induced proliferation and apoptosis in cardiac myxoma (CM) was not reported. In the present study, we used immnohistochemistry, immunoblotting, and qRT-PCR to detect the expression profile of IGF-1 and AEG-1 in 90 CM tissues, and then cultured CM cells were subjected to si-AEG-1, in vitro, and in vivo assays. Our findings showed that IGF-1 and AEG-1 were obviously upregulated in CM tissues and markedly associated with tumor size. When CM cells were treated with si-AEG-1, si-AEG-1 attenuated IGF-1-induced CM cell growth and enhanced cell apoptosis. Mechanically, we validated the expression of AEG-1, p-Erk1/2, and p-Akt increased in CM cells in response to IGF-1 treatment in a time-dependent manner. However, si-AEG-1 affected the expression of these proteins. Functionally, we found the knockdown of AEG-1-inhibited G1/S transition and tumor formation of CM cells. In conclusion, AEG-1 regulates IGF-1-induced proliferation and apoptosis via Erk1/2 and Akt signaling in CM development, which suggests IGF-1-AEG-1 signaling could be recommended to be a useful target to exert anti-tumor effects on CM.

Effect of postoperative oxygen therapy regimen modification on oxygenation in patients with acute type A aortic dissection.

Objective: In this study, we investigated the effect of various oxygen therapy regimens on oxygenation in patients with acute type A aortic dissection (AAD). Methods: A quasi-randomized controlled trial was conducted, in which patients with AAD hospitalized for surgery from June to September 2021 were assigned to the control group (patients received conventional oxygen therapy after postoperative mechanical ventilation, weaning, and extubation) and those who were admitted from October to December 2021 were assigned to the observation group [patients underwent optimally adjusted therapy based on the treatment of the control group, which mainly included prioritized elevation of positive end-expiratory pressure (PEEP) and restricted use of the fraction of inspired oxygen (FiO2)].The postoperative oxygenation index, blood gas analysis, and duration of mechanical ventilation were compared between the two groups. Results: There were significant differences in oxygenation observed at 2 h postoperatively between the groups. 12, 24, and 72 h postoperatively, the oxygenation index varied significantly between the two groups. There were statistically significant differences in the time effects of the oxygenation index and PaO2 between the two groups, as well as significant differences in the length of stay in the intensive care unit. Conclusion: For the postoperative care of patients with AAD, it is suggested that the minimum FiO2 required for oxygenation of patients be maintained. In addition, it is possible to enhance PEEP as a priority when PaO2 is low.

Multi-Functional Bio-HJzyme: Revolutionizing Diabetic Skin Regeneration with its Glucose-Unlocked Sterilization and Programmed Anti-Inflammatory Effects.

Antibacterial dynamic therapy (ADT) triggered by reactive oxygen species (ROS) is promising for diabetic infectious disease treatment. However, the limited local O2 /H2 O2 production and post-treatment inflammation remain long-standing issues. To address these challenges, a novel H2 -evolving bio-heterojunction enzyme (Bio-HJzyme) consisting of graphite-phase carbon nitride/copper sulfide (CN/Cu2-x S) heterojunction and glucose oxidase (GOx) is created. The Bio-HJzyme offers glutathione peroxidase (GPx), peroxidase (POD), and catalase (CAT) mimetic activities; provides anti-pathogen properties via programmed light activation; and effectively promotes diabetic wound healing. Specifically, its GPx-mimetic activity and the presence of GOx significantly enhance the yield of H2 O2 , which can be catalyzed through POD-mimetic activity to produce highly germicidal •OH. The H2 O2 can also be catalyzed to H2 O and O2 , assisted by the CAT-mimetic activity. The catalyzed products can then be catalyzed into germicidal •OH and •O2 - under NIR light irradiation, giving enhanced ADT. Further, CN can split water to form H2 under solar light, which dramatically suppresses the inflammation caused by excessive ROS. In vivo evaluation confirms that Bio-HJzyme promotes the regeneration of diabetic infectious skin through killing bacteria, enhancing angiogenesis, promoting wound bed epithelialization, and reinforcing anti-inflammatory responses; hence, providing a revolutionary approach for diabetic wounds healing.

Comparison of two techniques in proximal anastomosis in acute type A aortic dissection.

Background: The proximal anastomosis is an important procedure during the acute type A aortic dissection (AAAD) surgery. The conventional method is a double patch sandwich technique with Teflon felt. Adventitial eversion and prosthesis eversion technique as a novel approach has been applied to many patients in our center. Herein, This technique would be introduced, and the perioperative and 1-year follow-up results of the two different anastomosis methods were also evaluated. Methods: Between December 2017 and May 2021, 143 AAAD patients who underwent total arch replacement (TAR) and frozen elephant trunk (FET) implantation were included in this retrospective study. Patients were divided into the eversion technique group (adventitial eversion and prosthesis eversion technique for proximal anastomosis, n = 64) and the sandwich technique group (n = 79). Results: The medical records were analyzed and compared between the groups. The mean operation time was 466 ± 73 min in the eversion technique group and 513 ± 81 min in the sandwich technique group (P < 0.001). Compared with the sandwich technique group, the eversion technique group also showed a shorter time on proximal anastomosis (38 ± 12 min vs. 58 ± 20 min, P < 0.001), cardiopulmonary bypass (195 ± 26 vs. 211 ± 40 min, P = 0.003), and aortic cross-clamp (120 ± 23 min vs. 134 ± 27 min, P = 0.002). Furthermore, a decreased proportion of >600 ml fresh frozen plasmas transfusion was observed in eversion technique group (10.9% vs. 34.2%, P = 0.002). No statistical differences were found in the postoperative morbidities and 1-year follow-up outcomes. Conclusion: Proximal anastomosis with adventitial eversion and prosthesis eversion technique is a promising surgical option for AAAD patients, with favorable perioperative and 1-year follow-up results.

Early Outcomes of Left Subclavian Artery Revascularization Using Castor Single-Branched Stent-Graft in the Treatment of Type B Aortic Dissection or Intramural Hematoma.

BACKGROUND: More evidence was required to guide the management of left subclavian artery (LSA) during thoracic endovascular aortic repair (TEVAR). The present study aimed to compare the outcomes of LSA coverage with LSA revascularization. Another purpose of this study was to share our experience of LSA revascularization with castor single-branched stent-graft. METHODS: From January 2016 to December 2019, 134 patients with type B aortic dissection (TBAD) or intramural hematoma (IMH) were enrolled and divided into two groups, the LSA-covered group (n = 61) and the LSA-revascularized group (with castor single-branched stent-graft, n = 73). The results, such as in-hospital and 30-day mortality, stroke, paraplegia, left arm ischemia, operation time, endoleak, were compared between the two groups. RESULTS: The incidence of 30-day stroke in the LSA-covered group (8.2%) was significantly higher compared with the LSA-revascularized group (0%, P = 0.018). 30-day ischemia of left arm occurred in more patients in the LSA-covered group (11.5%, P = 0.003). No statistical difference was found in the incidences of paraplegia, endoleak, in-hospital mortality, and 30-day mortality. CONCLUSIONS: LSA should be revascularized during TEVAR to reduce the incidences of stroke and left arm ischemia. Castor single-branched stent-graft was feasible and safe for treating TBAD or IMH.

Endovascular Aortic Repair With Castor Single-Branched Stent-Graft in Treatment of Acute Type B Aortic Syndrome and Aberrant Right Subclavian Artery.

OBJECTIVE: In this retrospective study, we presented the results of Castor single-branched stent-graft in a small series of patients with acute type B aortic syndrome and aberrant right subclavian artery (ARSA). METHODS: Between January 2019 and November 2019, 5 patients were diagnosed with acute type B aortic syndrome and ARSA (4 patients with intramural hematoma and ARSA, 1 patient with type B aortic dissection and ARSA). All the patients underwent thoracic endovascular aortic repair (TEVAR) using Castor single-branched stent-graft. In-hospital and 3-month outcomes were collected. RESULTS: The mean operative time was 116 ± 20.43 minutes (range 90-145). All the TEVAR procedures were successfully performed without conversion to open surgery (100% success rate). All the ARSAs of the 5 patients were revascularized in situ by Castor single-branched stent-grafts. No deaths and complications were observed in the 3-month follow-up. The maximal diameters of diseased aortas in the 4 patients with IMH decreased 3 months after TEVAR. The false lumen in the graft-covered segment was completely thrombosed in the patient with type B aortic dissection. CONCLUSIONS: Castor single-branched stent-graft may be a good choice in treatment of acute type B aortic syndrome and aberrant right subclavian artery.

S-Nitrosylation of Prostacyclin Synthase Instigates Nitrate Cross-Tolerance In Vivo.

Development of nitrate tolerance is a major drawback to nitrate therapy. Prostacyclin (PGI2) is a powerful vasodilator produced from prostaglandin (PGH2) by prostacyclin synthase (PGIS) in endothelial cells. This study aimed to determine the role of PGIS S-nitrosylation in nitrate tolerance induced by nitroglycerin (GTN). In endothelial cells, GTN increased PGIS S-nitrosylation and disturbed PGH2 metabolism, which were normalized by mutants of PGIS cysteine 231/441 to alanine (C231/441A). Clearance of nitric oxide by carboxy-PTIO or inhibition of S-nitrosylation by N-acetyl-cysteine decreased GTN-induced PGIS S-nitrosylation. Enforced expression of mutated PGIS with C231/441A markedly abolished GTN-induced PGIS S-nitrosylation and nitrate cross-tolerance in Apoe-/- mice. Inhibition of cyclooxygenase 1 by aspirin, supplementation of PGI2 by beraprost, and inhibition of PGIS S-nitrosylation by N-acetyl-cysteine improved GTN-induced nitrate cross-tolerance in rats. In patients, increased PGIS S-nitrosylation was associated with nitrate tolerance. In conclusion, GTN induces nitrate cross-tolerance through PGIS S-nitrosylation at cysteine 231/441.

Concurrent true inferoposterior left ventricular aneurysm and ventricular septal rupture secondary to inferior myocardial infarction: a case report.

BACKGROUND: Although left ventricular aneurysm (LVA) is the most common mechanical complication of myocardial infarction (MI), it rarely involves the inferior or posterior left ventricular wall. Ventricular septal rupture (VSR) may be a fatal mechanical complication of MI but rarely occurs in the posterior or inferior portion of the interventricular septum. Thus, LVA and VSR as two mechanical complications of MI in the same patient are extremely rare. CASE SUMMARY: A 65-year-old woman, who had inferior ST-segment elevation myocardial infarction 2 months before without reperfusion therapy, was admitted with exertional dyspnoea for 1 month. Echocardiography and computed tomography revealed true inferoposterior LVA and VSR as concurrent complications of MI. These imaging findings were confirmed during cardiac surgery. After successful coronary bypass grafting and ventriculoplasty, the patient recovered quickly and was discharged from the hospital. DISCUSSION: A rare case of post-infarction inferoposterior LVA with concurrent interventricular septal rupture was reported. Transthoracic and transoesophageal echocardiography and cardiac computed tomography were valuable tools for the diagnosis of this rare condition. Combined coronary bypass grafting and ventriculoplasty were effective in treating this often fatal complication of inferior MI.

Oxygenation impairment after total arch replacement with a stented elephant trunk for type-A dissection.

OBJECTIVE: To study the risk factors of oxygenation impairment in patients with type-A acute aortic dissection who underwent total arch replacement with a stented elephant trunk. METHODS: In this study, 169 consecutive patients were enrolled who were diagnosed with type-A acute aortic dissection and underwent a total arch replacement procedure at the Qilu Hospital of Shandong University between January 2015 and February 2017. Postoperative oxygenation impairment was defined as arterial oxygen partial pressure/inspired oxygen fraction ≤ 200 with positive end expiratory pressure ≥ 5 cm H2O that occurred within 72 hours of surgery. Perioperative clinical characteristics of all patients were collected and univariable analyses were performed. Risk factors associated with oxygenation impairment identified by univariable analyses were included in the multivariable regression analysis. RESULTS: The incidence of postoperative oxygenation impairment was 48.5%. Postoperative oxygenation impairment was associated with prolonged mechanical ventilation time, intensive care unit stay, and hospital stay. Multivariable regression analysis demonstrated that body mass index (odds ratio [OR], 1.204; 95% confidence interval [CI], 1.065-1.361; P = .003), preoperative oxygenation impairment (OR, 9.768; 95% CI, 4.159-22.941; P < .001), preoperative homocysteine (OR, 1.080; 95% CI, 1.006-1.158; P = .032), circulatory arrest time (OR, 1.123; 95% CI, 1.044-1.207; P = .002), and plasma transfusion (OR, 1.002; 95% CI, 1.001-1.003; P = .002) were significantly associated with postoperative oxygenation impairment. CONCLUSIONS: Postoperative oxygenation impairment is a common complication of surgery for type-A acute aortic dissection. Body mass index, preoperative oxygenation impairment, preoperative homocysteine, circulatory arrest time, and plasma transfusion were independent risk factors for oxygenation impairment after a total arch replacement procedure.

[Effects of immunosuppressive treatment in prevention of calcification in aortic valved homograft: experiment with rats].

OBJECTIVE: To investigate the effects of immunosuppressive treatment in prevention of calcification in aortic valved homograft (AVH). METHODS: 120 Wistar rats were randomly divided into 4 equal groups: Group A (allogene group) undergoing incision of the abdominal aorta and implantation of the AVH with myocardial cuff from SD rats, Group B, injected with cyclosporine A intraperitoneally one day after the implantation, Group C, injected intraperitoneally with anti-dendritic cell monoclonal antibody (DCmAb) one day after the implantation, and Group D (isogenenic or control group), receiving the AVH of another Wistar rats. All groups were further subdivided into 5 equal subgroups to be sacrificed at different time points: 2, 4, 8, 12, and 16 weeks postoperatively. Blood samples were obtained from the vena cava to detect the expression of T-cell antigen receptor (TCR)-alpha and beta and CD28 by flow cytometry. AVH specimens were obtained to observe the changes of endotheliocytes and smooth muscle cells with light and electron microscopy. The expression of CD54 was detected by immunohistochemistry. The calcium content of the AVH tissue after transplantation was examined by flame atomic absorption spectrophotometry. RESULTS: (1) Compared with the isogenic group, the expression levels of TCR-alpha and beta and CD28 in the allogener groups were all significantly higher at all time points (all P < 0.01), peaked 2 approximately 4 weeks after operation, then gradually decreased, and approached the level of the controls 12 weeks after the implantation. Specifically, the expression levels of TCR-alpha and TCR-beta 2 and 4 weeks postoperatively of Group A were 52.4% +/- 3.3% and 43.8% +/- 6.4% respectively, significantly higher than those of Group B [(34.5 +/- 3.5)% and (31.6 +/- 2.6)% respectively], Group C [(31.6 +/- 2.3)% and (29.5 +/- 3.0)% respectively), and Group D (23.2 +/- 1.3)% and (21.6 +/- 2.3)% (all P < 0.01)]; and the CD28 expression level 2 approximately 4 weeks after operation of Group A were (51.7 +/- 7.5)% and (66.3 +/- 4.4)% respectively, both significantly higher than those of Group B [(41.2 +/- 1.6)% and (55.1 +/- 5.1)% respectively], Group C [(36.6 +/- 3.6)% and (51.8 +/- 5.6)% respectively], and Group D [30.7 +/- 1.4)% and (33.3 +/- 0.9)% respectively)] [all P < 0.01 except those levels 12 and 16 weeks after the operation in each subgroup (P > 0.05)] And the levels of TCR-alpha and TCR-beta and CD28 of the 2 treatment groups were all significantly lower than those of the untreated group (Group A) (all P < 0.01). (2) The calcium contents of the AVH tissues of Group A, B, and C significantly increased 4 weeks after the operation and peaked 12 and 16 weeks after operation. No significant difference in calcium level was found in Group D at different time points (all P > 0.05). The calcium contents in AVH tissues 4 and 8 weeks postoperatively of Groups A, B, and C were (2856 +/- 79) microg/g and (3587 +/- 168) microg/g respectively, (2518 +/- 73) microg/g, (3237 +/- 187) microg/g; and (2176 +/- 210) microg/g and (3089 +/- 176) microg/g; all significantly higher than those of Group D (860 +/- 60) microg/g and (870 +/- 50) microg/g respectively, all P < 0.01. CONCLUSION: Immunosuppressive treatment obviously reduces the immune rejection and delays the course of AVH calcification.

Hypoxia-inducible factor 1a induces phenotype switch of human aortic vascular smooth muscle cell through PI3K/AKT/AEG-1 signaling.

To date, hypoxia-inducible factor 1a (HIF-1a) and astrocyte elevated gene-1 (AEG-1) have been involved in the proliferation, migration and morphological changes of vascular smooth muscle cells. However, the potential relationship of HIF-1a-AEG-1 pathway in human aortic smooth muscle cell (HASMC) has not been reported. In the present study, in-vitro assays were utilized to explore the potential impact of HIF-1a-AEG-1 signaling on HASMC phenotype. Here, we found that HIF-1a expression was up-regulated in the media of thoracic aortic dissection tissues as compared with normal aortic tissues, and was associated with increased apoptotic SMCs and decreased AEG-1 expression. Mechanically, hypoxia promoted the expression of HIF-1a by PI3K-AKT pathway in HASMCs; HIF-1a further suppressed the expressions of AEG-1, a-SMA and SM22a, and promoted osteopontin (OPN) expression. Functionally, HIF-1a inhibited the proliferation and migration of HASMCs. However, si-HIF-1a or Akt inhibitor abrogated HIF-1a-mediated related expressions and biological effects above. In conclusion, HIF-1a induces HASMC phenotype switch, and closely related to PI3K/AKT and AEG-1 signaling, which may provide new avenues for the prevention and treatment of aortic dissection diseases.

Pravastatin activates activator protein 2 alpha to augment the angiotensin II-induced abdominal aortic aneurysms.

We have previously reported that activation of AMP-activated kinase alpha 2 (AMPKα2) by nicotine or angiotensin II (AngII) instigates formation of abdominal aortic aneurysms (AAA) in Apoe-/- mice. Statins, used to treat hyperlipidemia widely, activate AMPK in vascular cells. We sought to examine the effects of pravastatin on AAA formation and uncover the molecular mechanism. The AAA model was induced by AngII and evaluated by incidence, elastin degradation, and maximal abdominal aortic diameter in Apoe-/- mice. The phosphorylated levels of AMPKα2 and activator protein 2 alpha (AP-2α) were examined in cultured vascular smooth muscle cells (VSMCs) or in mice. We observed that pravastatin (50 mg/kg/day, 8 weeks) remarkably increased the AngII-induced AAA incidence in mice. In VSMCs, pravastatin increased the levels of pAMPK, pAP-2α, and MMP2 in both basal and AngII-stressed conditions, which were abolished by tempol and compound C. Pravastatin-upregulated MMP2 was abrogated by AMPKα2 or AP-2α siRNA. Lentivirus-mediated gene silence of AMPKα2 or AP-2α abolished pravastatin-worsened AAA formations in AngII-infused Apoe-/- mice. Clinical investigations demonstrated that both AMPKα2 and AP-2α phosphorylations were increased in AAA patients or human subjects taking pravastatin. In conclusion, pravastatin promotes AAA formation through AMPKα2-dependent AP-2α activations.