Macrophage ILF3 promotes abdominal aortic aneurysm by inducing inflammatory imbalance in male mice.

Imbalance of proinflammatory and anti-inflammatory responses plays a crucial role in the progression of abdominal aortic aneurysms. ILF3, a known modulator of the innate immune response, is involved in cardiovascular diseases. This study aims to investigate the role of ILF3 in abdominal aortic aneurysm formation. Here, we use multi-omics analyzes, transgenic male mice, and multiplex immunohistochemistry to unravel the underlying involvement of ILF3 in abdominal aortic aneurysms. The results show that macrophage ILF3 deficiency attenuates abdominal aortic aneurysm progression, while elevated macrophage ILF3 exacerbates abdominal aortic aneurysm lesions. Mechanistically, we reveal that macrophagic ILF3 increases NF-κB activity by hastening the decay of p105 mRNA, leading to amplified inflammation in macrophages. Meanwhile, ILF3 represses the anti-inflammatory action by inhibiting the Keap1-Nrf2 signaling pathway through facilitating the ILF3/eIF4A1 complex-mediated enhancement of Keap1 translational efficiency. Moreover, Bardoxolone Methyl treatment alleviates the severity of abdominal aortic aneurysm lesions in the context of elevated ILF3 expression. Together, our findings underscore the significance of macrophage ILF3 in abdominal aortic aneurysm development and suggest its potential as a promising therapeutic target for abdominal aortic aneurysms.

Low preoperative serum fibrinogen level is associated with postoperative acute kidney injury in patients with in acute aortic dissection.

OBJECTIVE: Acute kidney injury (AKI) after cardiac surgery is associated with serious complication and high risk of mortality. The relationship between hemostatic system and the prognosis of patients with acute type A aortic dissection (ATAAD) has not been evaluated. The purpose of this study was to investigate the association between preoperative serum fibrinogen level and risk of postoperative AKI in patients with ATAAD. METHODS: A total of 172 consecutive patients undergoing urgent aortic arch surgery for ATAAD between April 2020 and December 2021 were identified from Beijing Anzhen Hospital aortic surgery database. The primary outcome was postoperative AKI as defined by the Kidney Disease Improving Global Outcomes (KDIGO) criteria. The univariate and multivariate logistic regression analysis were done to assess the independent predictors of risk for postoperative AKI. Receiver operating characteristic (ROC) curve was generated to evaluate the predictive probabilities of risk factors for AKI. RESULTS: In our study, 51.2% (88/172) patients developed postoperative AKI. Multivariate logistic regression analysis identified low preoperative serum fibrinogen level (OR, 1.492; 95% CI, 1.023 to 2.476; p = 0.021) and increased body mass index (BMI) (OR, 1.153; 95% CI, 1.003 to 1.327; p = 0.046) as independent predictors of postoperative AKI in patients with ATAAD. A mixed effect analysis of variance modeling revealed that obese patients with low preoperative serum fibrinogen level had higher incidence of postoperative AKI (p = 0.04). The ROC curve indicated that low preoperative serum fibrinogen level was a significant predictor of AKI [area under the curve (AUC), 0.771; p < 0.001]. CONCLUSIONS: Low preoperative serum fibrinogen level and obesity were associated with the risk of postoperative AKI in patients with ATAAD. These data suggested that low preoperative serum fibrinogen level was preferred marker for predicting the postoperative AKI, especially in obese patients with ATAAD.

High-TSH Subclinical Hypothyroidism Is Associated With Postoperative Mortality in Acute Type A Aortic Dissection.

Background: Subclinical hypothyroidism can negatively affect the cardiovascular system and increase the risk of mortality, especially for individuals with thyroid-stimulating hormone (TSH) levels above 10 mU/L. We investigated the relationship between high-TSH subclinical hypothyroidism and postoperative mortality in acute type A aortic dissection (ATAAD) patients. Method: We enrolled 146 patients with ATAAD who underwent aortic surgery in Beijing Anzhen Hospital from July 2016 to November 2018. Thyroid hormone levels were obtained before surgery, and participants were divided into a ≥10mU/L TSH level group and a <10mU/L level group. Cox proportional hazard regression and subgroup analysis were conducted to examine the association of preoperative high-TSH subclinical hypothyroidism with postoperative mortality. Result: Participants with preoperative high-TSH (≥10mU/L) subclinical hypothyroidism tended to have longer hospitalization stays after surgery [16.0 (IQR 11.0-21.0) days vs 12.5 (IQR 8.0-16.0) days, P=0.001]. During the first 30 days after operation, 15 of 146 patients died (10.3%); during a median of 3.16 (IQR 1.76-4.56) years of follow-up, 24 patients died (16.4%). Cox proportional hazard regression showed that preoperative high-TSH subclinical hypothyroidism was independently associated with 30-day mortality (HR=6.2, 95% CI, 1.7-22.0, P=0.005) and postoperative mortality after adjusting for age, sex, BMI, hypertension, ejection fraction, diabetes and history of PCI (HR=3.4, 95% CI, 1.4-8.0, P=0.005). Conclusion: This study showed that preoperative high-TSH subclinical hypothyroidism was an independent predictor of postoperative mortality in ATAAD patients who underwent aortic surgery.

Renal Artery Partial Occlusion After Aortic Dissection Is Associated With Impaired Renal Function in the Affected Kidney.

BACKGROUND: The renal artery is often involved in aortic dissection, leading to kidney ischaemia and renal dysfunction. However, some patients with aortic dissection with combined renal artery involvement do not show clinical renal dysfunction. This study aimed to analyse the relationship between renal artery involvement and renal function. METHODS: Data and images were collected from 79 patients (Group A), in Beijing Anzhen hospital between January 2015 and December 2017, who had type A aortic dissection, in order to analyse the relationship between renal artery involvement and serum creatinine. In order to further analyse the relationship between renal artery involvement and single kidney function, data from 27 patients (Group B) with aortic dissection from August 2018 to October 2018 were collected. Renal dynamic imaging was conducted, and clinical and image data were recorded. RESULTS: Results showed that patients with one partially occluded renal artery had higher variance of serum creatinine after surgery compared with patients with one false-lumen renal artery (5.8±22.7 µmol/L vs -18.7±22.7 µmol/L; p=0.003). The glomerular filtration rate of a single kidney that had a partially occluded renal artery was lower than that of a single kidney with a normal renal artery (37.77±9.57 vs 42.73±10.54; p=0.04). CONCLUSIONS: A partially occluded renal artery in aortic dissection was associated with impaired renal function after surgery, even though patients did not present high serum creatinine. More attention should be paid to those experiencing aortic dissection.

Sun's total arch replacement and stent elephant trunk with modified branch-first technique for patients with Stanford type A aortic dissection.

BACKGROUND: Stanford type A aortic dissection (STAAD) is a critical cardiovascular disease, and surgical procedure is the first-choice treatment. The classical surgical procedure still leads to a high mortality rate and neurological complications. In this study, we introduce a new modified Sun's procedure and investigate the association between the branch-first technique and the postoperative outcomes of patients with STAAD. METHODS: A total of 108 consecutive patients with STAAD who underwent arch replacement and stent elephant trunk procedure at Beijing Anzhen Hospital between July, 2017 and November, 2018 were included in the analysis. The patients were divided into two groups: the branch-first group and the classic group. The branch-first group and the classic group comprised 24 patients (22.2%) and 84 patients (77.8%), respectively. RESULTS: Patients in the branch-first group had a significantly shorter cardiopulmonary bypass (CPB) duration (172.4±29.9 vs. 194.9±47.4 min; P=0.035), Intensive care unit (ICU) stay [17.0 (14.6-38.2) vs. 42.1 (19.7-87.2) hours; P<0.001], and mechanical ventilation time [15.5 (11.9-40.0) vs. 19.0 (17.0-45.6) hours; P=0.018] than patients in the classic group. The branch-first was associated with a reduction in postoperative neurological complications in all models. CONCLUSIONS: The benefits of the branch-first technique, including lower CPB duration, better bilateral cerebral perfusion, and higher nasopharyngeal temperature during hypothermic arrest, contributed to a shortened recovery time for patients after surgery.

Ascending aortic dilation in adult patients with congenital ventricular septal defect: An observational study.

Many adult patients with congenital ventricular septal defect (VSD) also developed ascending aortic dilation, but few report the clinical features and surgical management of these patients. This study was designed to study ascending aortic dilation in adult patients with congenital VSD, and summarized the treatment experience and prognosis.To assess the clinical features and surgical management, we performed a retrospective analysis on preoperative data, intraoperative data, and postoperative data from the adult patients with congenital VSD who developed ascending aortic dilation in our institution from February 2010 to December 2016.From February 2010 to December 2016, we operated on 13 adult patients (12 males, 92.31%) with VSD who developed ascending aortic dilation. Median age was 37 (interquartile range 14) years. All patients suffered from perimembranous VSD and received surgical treatment. Their symptoms were all improved after surgery, no deaths occurred.Surgery is feasible for the ascending aortic dilation in adult patients with congenital VSD. Both proper perioperative treatment and close monitoring are required for the successful surgery.

CD40L promotes development of acute aortic dissection via induction of inflammation and impairment of endothelial cell function.

Acute aortic dissection is one of the most lethal cardiovascular disease. The major histopathological feature of AAD is medial degradation, especially breakdown of elastin and collagen. However, the underlying mechanism remains a mystery. Platelets expressed CD40 Ligand (CD40L) is recently recognised as a key effector of cardiovascular disease development through its pro-inflammatory effect. To clarify the role of CD40L in AAD, we examined level of CD40L in human blood serum samples and found that it is significantly higher in AAD patients compared with healthy subjects (26.8±5.52 ng/mL versus 13.4±4.00 ng/mL). To further investigate if CD40L is involve in the development of AAD, we applied ß-aminopropionitrile (BAPN) induced mouse model of AAD. Consistent with the human data, circulating CD40L in AAD mice much higher than normal mice (148.40±75.96 pg/mL versus 44.09±19.65 pg/mL). Meanwhile, multiple pro-inflammatory chemokines significantly increased in AAD mice. Importantly, the CD40L-/- mice treated with BAPN did not develop these phenotypes. Lastly, we confirmed that endothelial cells migration was significantly inhibited by CD40L, suggesting impaired recovery from intimal injury. In summary, we found that CD40L promoted AAD development through its pro-inflammatory effects and inhibition of endothelial cell function.

Elevated D-dimer increases the risk of dialysis after surgery in patients with Stanford A aortic dissection through the impact of the coagulation system.

BACKGROUND: To investigate whether Elevated D-dimer increases the risk of dialysis after surgery in patients with Stanford A aortic dissection. METHODS: A total of 120 patients with type A aortic dissection who underwent surgery at our institution from August 2014 to December 2015 were enrolled in the study. Acute type A aortic dissection was treated with Sun's operation. Blood samples were collected before anesthesia induction, 4 hours after surgery, and 24 hours after surgery. Patients were divided into two groups according to their D-dimer levels. Group A had D-dimer concentrations below 3,000 µg/L; Group B had D-dimer concentrations above 3,000 µg/L. RESULTS: Group A (n=99; 82.5% of total patients) had D-dimer levels below 3,000 µg/L. Eighteen patients in Group A (18.18%) died within 30 days after surgery. Group B (n=21; 18.5% of total patients) had D-dimer levels above 3,000 µg/L. Seven patients in Group B (28%) died within 30 days after surgery. A significantly higher percentage of patients in Group B had acute renal failure and the application of continuous renal replacement therapy (P=0.02). There were significant differences between the groups in intraoperative blood loss (P=0.001) and hemostatic drugs administered, such as intraoperative prothrombin complex (P=0.015). The D-dimer (P<0.001), FIB (P=0.008) and FDP (P<0.001) in the B group were significantly higher than those in the A group, but there was no significant difference between the 4 hours after the operation and the 24 hours after the operation. Thromboelastogram (TEG) examination showed that preoperative R in group B was shorter than the A group, 4 hours after operation was still lower in group B than in group A. Through ROC analysis, D-dimer is a prognostic indicator for postoperative renal failure. When cut-off =1,039.00, sensitivity =91.7%, specificity =54.2%. When D-dimer is below 1,039 µg/L, the risk of dialysis after surgery in patients with Stanford A aortic dissection is low. Prognostic value of D-dimer was evaluated using ROC analysis and the results showed that the area under curve (AUC) of D-dimer as prognostic indicator for postoperative renal failure was 0.741 (95% CI, 0.642-0.840; P value<0.001). Stepwise binary logistic regression analysis revealed that total suspended red, wakefulness delayed, D-dimer were independent predictors of dialysis risk after surgery in patients with Stanford A aortic dissection among all the other factors. CONCLUSIONS: D-dimer above 3,000 µg/L increases the risk of dialysis after surgery in patients with Stanford A aortic dissection through the impact of the coagulation system. When D-dimer is below 1,039 µg/L, the risk of dialysis after surgery in patients with Stanford A aortic dissection is low.

Treatment of patients with aortic disease during pregnancy and after delivery.

Objective This study aimed to review treatment of patients with aortic disease during pregnancy and after delivery in Beijing Anzhen Hospital. Methods A retrospective study was conducted using data from 12 patients with aortic disease during pregnancy and after delivery in our institution from May 2005 to December 2014. Patients were provided different treatments based on the type of aortic disease and clinical characteristics. Results The mean age was 29.83 ± 4.17 years, mean height was 171.7 ± 8.22 cm, mean weight was 68.55 ± 10.62 kg, and mean body mass index was 23.18 ± 2.93 kg/m2. Two patients with Stanford type A aortic dissection died of renal failure after surgery. All of the other patients were discharged. Six foetuses survived. One patient continued her pregnancy after an aortic operation. The gestational age of the remaining five patients was less than 28 weeks at the time of the operation and all foetuses of these five patients died. Conclusions A suitable treatment strategy for aortic disease during pregnancy and after delivery should be chosen based on an individual's comprehensive clinical condition. Foetal management should be chosen based on gestational age and severity of aortic disease.

Innominate artery aneurysm, how to solve it?

We herein describe our *These authors contributed equally to this work. experience with a congenital innominate artery aneurysm (IAA) that was managed with a simple surgical procedure. A 44-year-old woman was admitted for chest distress. Computed tomography angiography showed a 3.6-cm IAA arising from the aortic arch and compressing the trachea. A median sternotomy was performed with the patient under general anesthesia, and the IAA was found to involve the origin of the innominate artery and the bifurcation of the right subclavian artery and common carotid artery; however, the aorta was intact. An 8-mm Dacron graft was anastomosed to the ascending aorta and distal end of the IAA without cardiopulmonary bypass. The postoperative course was uneventful, and repeat computed tomography angiography revealed no evidence of recurrence 6 months postoperatively. We also herein present a literature review of this rare clinical condition.

Disruption of mechanical stress in extracellular matrix is related to Stanford type A aortic dissection through down-regulation of Yes-associated protein.

In this study, we assessed whether the down-regulation of Yes-associated protein (YAP) is involved in the pathogenesis of extracellular matrix (ECM) mechanical stress-induced Stanford type A aortic dissection (STAAD). Human aortic samples were obtained from heart transplantation donors as normal controls and from STAAD patients undergoing surgical replacement of the ascending aorta. Decreased maximum aortic wall velocity, ECM disorders, increased VSMC apoptosis, and YAP down-regulation were identified in STAAD samples. In a mouse model of STAAD, YAP was down-regulated over time during the development of ECM damage, and increased VSMC apoptosis was also observed. YAP knockdown induced VSMC apoptosis under static conditions in vitro, and the change in mechanical stress induced YAP down-regulation and VSMC apoptosis. This study provides evidence that YAP down-regulation caused by the disruption of mechanical stress is associated with the development of STAAD via the induction of apoptosis in aortic VSMCs. As STAAD is among the most elusive and life-threatening vascular diseases, better understanding of the molecular pathogenesis of STAAD is critical to improve clinical outcome.

Surgery for mitral regurgitation in patients with aortic root aneurysm: Transaortic or transseptal approach?

OBJECTIVE: Mitral regurgitation is common in patients with aortic root aneurysm. Mitral valve repair (MVP) or replacement (MVR) can be performed for these patients through either a transverse aortotomy (TA) or transseptal approach (TS). This study sought to compare the early outcomes of mitral valve surgery through the TA and TS approaches and decide which is optimal for this subset of patients. METHODS: Between March 2013 and April 2015, we operated on 99 patients (81 males, 81.8%) with aortic root aneurysm who developed mitral regurgitation. Mean age was 47.8±16.5years. MVR was performed in 66 patients (TAR=27; TSR=39) and MVP in 33 (TAP=8; TSP=25). The baseline and operative outcomes data were compared between patients with MVR and MVP through the TA vs TS approaches. RESULTS: Preoperatively, the mitral regurgitation area was significantly larger in the MVR than MVP groups (8.9±2.0 vs 7.8±3.8 cm2, p=0.0009), and in the TSP vs TAP groups (8.5±4.1 vs 5.6±1.3cm2, p=0.0049), but no significant difference was found between the TAR and TSR groups (8.7±2.2 vs 9.0±1.8cm2, p=0.4681); the aortic sinus size was significantly larger in the TAR than TSR group (66.7±15.8 vs 52.1±8.8mm, p=0.0061). Subvalvular structure was preserved in 12 MVR patients (18.2%). In MVP patients, Kay annuloplasty was used in 11 (33.3%) and annuloplastic ring in 22 (66.7%). The times of cardiopulmonary bypass (CPB) and cross-clamp in patients with TA approach were significantly shorter compared to those with the TS approach (139±34 vs 176±38min, p=0.0001; 101±26 vs 129±31min, p=0.0002). No cases of mortality, stroke and renal failure occurred in the whole series. The amount of transfusion, lengths of ICU and hospital stay did not differ between patients with MVR and MVP, and between the TA and TS approaches. CONCLUSIONS: Both the TA and TS approaches achieved good early outcomes in MV surgery for patients with root aneurysm. The transverse aortotomy was associated with shorter CPB and cross-clamp times. Surgical approaches should be selected according to the underlying mitral valve etiology and the size of the aortic root.

Changes in the Hemostatic System of Patients With Acute Aortic Dissection Undergoing Aortic Arch Surgery.

BACKGROUND: Aortic arch surgery for patients with acute aortic dissection is frequently complicated by excessive bleeding and transfusion of allogeneic blood products. However, the physiopathology of acute aortic dissection and surgery-induced coagulopathy has never been precisely studied. The aim of the present study is to describe the changes of the perioperative hemostatic system in patients with acute aortic dissection undergoing aortic arch surgery. METHODS: Sixty-two patients undergoing emergent aortic arch surgery for Stanford type A acute aortic dissection were enrolled in this study from January 2013 to September 2014. The hemostatic system was evaluated using standard laboratory tests, plasma fibrinogen levels, and thromboelastogragh at 5 time points: anesthesia induction (T0), lowest nasopharyngeal temperature (T1), protamine reversal (T2), 4 h after surgery (T3), and on the first postoperative day (T4). RESULTS: The study results revealed that clotting factors had a tendency to be consumed in the preoperative period. Surgery and hypothermia resulted in a progressive reduction in clotting factors, platelet counts, and function, as well as fibrinogen concentration and function. After hemostatic therapy, although platelet counts were constantly low, clotting factors and platelet function returned to nearly preoperative levels. In contrast, fibrinogen concentration and function were still significantly lower than preoperative levels. CONCLUSIONS: The results of this prospective analysis showed that acute aortic dissection itself activated the hemostatic system even before surgery. After hemostatic therapy, fibrin formation was more impaired than platelet function. In this setting, we proposed that hemostatic therapy should focus on rapid and sufficient supplementation of fibrinogen. Thus, we recommend further increases in fibrinogen concentration to improve coagulopathy in patients with acute aortic dissection.

Is autologous or heterologous pericardium better for valvuloplasty? A comparative study of calcification propensity.

Pericardial calcification is detrimental to the long-term durability of valvuloplasty. However, whether calcification susceptibility differs between heterologous and autologous pericardium is unclear. In this study, we compared the progression of calcification in vivo between autologous and heterologous pericardium. We randomly divided 28 rabbits into 4 equal groups. Resected rabbit pericardium served as autologous pericardium, and commercial bovine pericardium served as heterologous pericardium. We subcutaneously embedded one of each pericardial patch in the abdominal walls of 21 of the rabbits. The 7 control rabbits (group A) received no implants. The embedded samples were removed at 2 months in group B, at 4 months in group C, and at 6 months in group D. Each collected sample was divided into 2 parts, one for calcium-content measurement by means of atomic-absorption spectroscopy, and one for morphologic and histopathologic examinations. When compared with the autologous pericardium, calcium levels in the heterologous pericardium were higher in groups B, C, and D (P <0.0001, P <0.0002, and P <0.0006, respectively). As embedding time increased, calcium levels in the heterologous pericardium increased faster than those in the autologous, especially in group D. Disorganized arrangements of collagenous fibers, marked calculus, and ossification were seen in the heterologous pericardium. Inflammatory cells-mainly lymphocytes and small numbers of macrophages-infiltrated the heterologous pericardium. The autologous pericardium showed a stronger ability to resist calcification. Our results indicate that autologous pericardium might be a relatively better choice for valvuloplasty.

Paris chinensis dioscin induces G2/M cell cycle arrest and apoptosis in human gastric cancer SGC-7901 cells.

AIM: To investigate the anti-tumor effects of Paris chinensis dioscin (PCD) and mechanisms regarding cell cycle regulation and apoptosis in human gastric cancer SGC-7901 cells. METHODS: Cell viability was analyzed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay. Cell apoptosis was evaluated by flow cytometry and laser scanning confocal microscope (LSCM) using Annexin-V/propidium iodide (PI) staining, and the cell cycle was evaluated using PI staining with flow cytometry. Intracellular calcium ions were detected under fluorescence microscope. The expression of cell cycle and apoptosis-related proteins cyclin B1, CDK1, cytochrome C and caspase-3 was measured by immunohistochemical staining. RESULTS: PCD had an anti-proliferation effect on human gastric cancer SGC-7901 cells in a dose- and time-dependent manner. After treatment of SGC-7901 cells with PCD, apoptosis appeared in SGC-7901 cells. Morphological changes typical of apoptosis were also observed with LSCM by Annexin V/PI staining, and the cell number of the G0/G1 phase was decreased, while the number of cells in the G2/M phase was increased. Cell cycle-related proteins, such as cyclin B1 and CDK1, were all down-regulated, but caspase-3 and cytochrome C were up-regulated. Moreover, intracellular calcium accumulation occurred in PCD-treated cells. CONCLUSION: G2/M phase arrest and apoptosis induced by PCD are associated with the inhibition of CDK-activating kinase activity and the activation of Ca(2+)-related mitochondrion pathway in SGC-7901 cells.