Suppression of nuclear factor-kappa B and mitogen-activated protein kinase signalling pathways by goshonoside-F5 extracted from Rubi Fructus.

Rubi Fructus, a traditional Chinese medicine, was considered as an anti-inflammatory agent in folk medicine. In the present study, we investigated the signalling pathways involved in the anti-inflammatory effects of goshonoside-F5 (GF5), isolated from Rubi Fructus, in peritoneal macrophages and examined its therapeutic effect in a mouse endotoxic shock model. GF5 decreased NO and PGE2 production in LPS-stimulated macrophages (IC50=3.84 and 3.16µM). This effect involved the suppression of NOS-2 and COX-2 gene expression at the transcriptional level. Examination of the effects of GF5 on NF-κB signalling demonstrated that it inhibits the phosphorylation of IκB-α and IκB-ß, blocking their degradation and the nuclear translocation of the NF-κB p65 subunit. Moreover, inhibition of MAPK signalling was also observed, and phosphorylation of p38 and JNK was suppressed in the presence of GF5. Inflammatory cytokines, including IL-6 and TNF-α, were down-regulated by this compound after activation with LPS (IC50=17.04 and 4.09µM). Additionally, GF5 (30 and 90mg/kg, i.p.) significantly reduced the circulating cytokine levels (IL-6 and TNF-α) and increased survival in a mouse model of endotoxemia. These results show that GF5 significantly inhibits the pro-inflammatory response induced by LPS, both in vitro and in vivo. Our results provide a strong pharmacological basis for further understanding the potential therapeutic role of GF5 in inflammatory disease and shed new light on the bioactivity of ent-labdane diterpene glucoside.

Endovascular stent placement for treatment of spontaneous isolated dissection of the superior mesenteric artery.

BACKGROUND: Spontaneous isolated dissection of the superior mesenteric artery (SIDSMA) is a rare condition often associated with a poor prognosis. The goal of this study is to assess the efficacy of endovascular treatment of SIDSMA with stenting and investigate the possible therapeutic mechanisms involved. METHODS: This is a retrospective review of all patients undergoing endovascular treatment of SIDSMA from January 2009 to December 2011. Patient demographics, history, clinical presentation, laboratory tests, image characteristics, endovascular treatments, and follow-up outcome were analyzed. RESULTS: Twenty-four patients with symptoms were treated. All except 1 patient (23 of 24, 96%) underwent successful stent placement (16 with single stent and 7 with overlapping stents). A total of 30 stents (4 balloon-expanded and 26 self-expanding) were placed during the procedures. In the perioperative period and during follow-up, symptom relief was achieved in 20 (83%) patients, and abdominal pain remained unchanged in 4 (17%). No death or serious complications occurred. The median length of hospital stay and follow-up was 3.25 ± 2.23 days (range 2-7 days) and 13.15 ± 8.27 months (range 6-23 months), respectively. Computed tomography angiography (CTA) performed 6 months postoperatively revealed stent patency in 23 cases (100%), false lumen patency in 5 cases (22%), and new development of dissection in the SMA distal to the stent in 1 case (4%). No significant differences were observed in the incidence of false lumen patency between patients treated with a single stent and those treated with overlapping stents, and between patients with and without symptom relief (P > 0.05 for both). CONCLUSIONS: For symptomatic SIDSMA patients without intra-abdominal hemorrhage and intestinal infarction, endovascular stent placement is a feasible treatment choice with a high success rate and good clinical outcome. Overlapping stenting may be proposed for patients with aneurysmal dilation. False lumen patency may occur in some cases during follow-up, but it does not affect improvement of SIDSMA symptoms.

Endovascular management of pararenal aortic aneurysms with multiple overlapping uncovered stents.

OBJECTIVE: This study aims at evaluating the safety and efficacy of a porous stent system consisting of multiple overlapping uncovered stents in the treatment of complex aortic aneurysms with vital branches. METHODS: Data of all patients with aortic aneurysms treated in our center with multiple overlapping uncovered stents between February 2010 and December 2011 were retrospectively reviewed. Preoperative characteristics, intraoperative details, and follow-up outcomes were documented. Technical success was defined as successful deployment of the stents to target locations without procedure-related complications. Clinical success was characterized by complete shrinkage or stabilization of the aneurysm, preservation of vital branches, and absence of major complications. Patients were grouped, according to rapidity of aneurysm thrombosis, into fast-thrombosis group (complete thrombosis of aneurysmal sac was achieved in ≤6 months) and a delayed-thrombosis group (>6 months required for complete thrombosis). Possible factors affecting the speed of thrombosis were analyzed statistically with the Fisher exact test and the t-test. RESULTS: This porous stent system was used to treat 34 patients (23 men, 11 women; mean age, 65.7 years). Technical success was achieved in all patients (100%). Regular follow-up over 6 months was achieved in 29 patients (mean length of follow-up, 11.4 months). Complete thrombosis of the aneurysm sac within 12 months was observed in 24 patients (83%). Aneurysm shrinkage was documented in seven patients (24%) and stabilization in 21 (72%). All branch arteries covered by bare stents stayed patent during follow-up. The overall clinical success rate reached 97% in the follow-up group. Risk factors for delayed thrombosis included fewer stents implanted (P = .013), longer sac entrance (P = .043), and use of antiplatelet medication (P = .040). CONCLUSIONS: An alternative method of management of complicated aortic aneurysm appears to be feasible using overlapping bare stents, which may prevent aneurysm growth while preserving vital branches. The short-term outcome of our study seems encouraging but is not sufficient to draw a robust conclusion. Further hemodynamic and clinical studies are warranted to evaluate long-term efficacy.

Multiple overlapping bare stents for endovascular visceral aneurysm repair: a potential alternative endovascular strategy to multilayer stents.

BACKGROUND: Multilayer stent has become a new endovascular strategy for visceral artery aneurysm repair. However, its use was not allowed in some areas, such as China. This study evaluates an alternative method: multiple overlapping bare stents for repairing visceral artery aneurysms. METHODS: Twenty-four patients with celiac artery aneurysm (n = 2), splenic artery aneurysm (n = 8), hepatic artery aneurysm (n = 3), superior mesenteric artery aneurysm (n = 6), and renal artery aneurysm (n = 5) were treated with 2 to 4 overlapping bare stents. Long-term results, including clinical achievement ratio and target artery patency, were followed up with computed tomographic angiography. RESULTS: Insertion of overlapping bare stents was successful in all patients. Five aneurysms (21%) were totally excluded 3 months after operation, increasing to 12 (50%) and 20 (83%) aneurysms with total isolation at 6 and 12 months' follow-up, respectively. The clinical achievement ratios of multiple overlapping bare stents on splenic artery aneurysms, hepatic artery aneurysms, renal artery aneurysms, celiac artery aneurysms, and superior mesenteric artery aneurysms were 75%, 100%, 80%, 50%, and 100%, respectively. All cases combined had 100% target artery patency. CONCLUSIONS: Preliminary experience showed that repair using multiple overlapping bare stents seemed to be a potential alternative strategy for treating visceral artery aneurysm, resulting in target artery patency. However, the exact mechanism requires further study and more cases should be involved.

[Biomechanical properties study of aorta in ß-aminopropionitrile-induced rat model].

OBJECTIVE: To investigate thoracic aortic longitudinal elastic strength in ß-aminopropionitrile (BAPN) treated rat model of aortic dissection (AD). METHODS: Twenty-nine young rats (Sprague-Dawley) were divided into tow groups, control group (n = 12) and BAPN group (n = 17). Seventeen rats were treated with 0.25% BAPN mixed in feed for 6 weeks. All the rats were sacrificed in the end of experiment and aorta was harvested for biomechanical and pathological study. Longitudinal elastic strength and stress were detected and analyzed by material testing machine. Elasticity modulus as well as maximum stretching length, draw ratio, maximum load, maximum strength, and maximum extensibility was calculated according to the analysis with thickness and area of aortic media. RESULTS: Nine BAPN-treated rats died of aortic dissecting aneurysm rupture during the experiment. The diameter of the aneurysms was (6.33 ± 1.17) mm and the length was (9 ± 5) mm. The maximum diameter significantly increased in BAPN-induced rats with AD (group B2) compared with without AD (group B1) and control group ((6.49 ± 1.20) mm vs. (1.45 ± 0.11), (1.25 ± 0.26); F = 165.257, P = 0.001 and 0.000, respectively), but there was no significance between group B1 and control group (P = 0.108). Thickness and area of aortic media in BAPN-induced rats significantly increased compared with control group (F = 27.277 and 27.153, P = 0.000 and 0.000, respectively), but there was no significance of area between group B1 and B2 (P = 0.540). Maximum stretching length, draw ratio, maximum load, maximum strength maximum extensibility and elasticity modulus were significantly decreased from group B2, group B1 to control group (P < 0.01, respectively). CONCLUSIONS: This study built a successful model of AD. Biomechanical analysis and the decrease of maximum stretching length, draw ratio, maximum load, maximum strength maximum extensibility and elasticity modulus may explain the formation of AD partly.

Overexpression of interleukin-1ß and interferon-γ in type I thoracic aortic dissections and ascending thoracic aortic aneurysms: possible correlation with matrix metalloproteinase-9 expression and apoptosis of aortic media cells.

OBJECTIVE: To examine the expression of interleukin-1ß and interferon-γ and their possible roles in aortic dissections and aneurysms. METHODS: Aortic specimens were obtained from patients with type I thoracic aortic dissection, ascending thoracic aortic aneurysms, and control organ donors. The expression of interleukin-1ß, interferon-γ, matrix metalloproteinase-9, and signal transduction factors phospho-p38 and phosphorylated c-jun N-terminal kinase (phospho-JNK) were detected by real time reverse transcription-polymerase chain reaction (real time RT-PCR), Western blot, and immunohistochemistry, respectively. Terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) staining was performed to detect apoptosis of media cells. The correlation of these factors and apoptosis was also studied. RESULTS: Apoptosis in the media of thoracic aortic dissection and in ascending thoracic aortic aneurysms was dramatically higher than in the control group. The expression of interleukin-1ß gradually increased from the control group, thoracic aortic dissection to ascending thoracic aortic aneurysms (p < 0.01, respectively). The expression of interferon-γ and matrix metalloproteinase-9 was significantly increased in the media of thoracic aortic dissection and ascending thoracic aortic aneurysms compared with the control group (p < 0.01, respectively). There were positive correlations between interleukin-1ß versus matrix metalloproteinase-9, interleukin-1ß versus phospho-p38 in thoracic aortic dissection (p < 0.01, respectively), and interferon-γ versus matrix metalloproteinase-9, interferon-γ versus phospho-JNK, interferon-γ versus apoptosis, and interleukin-1ß versus apoptosis in ascending thoracic aortic aneurysms (p = 0.02, 0.02, p < 0.01, p < 0.01). CONCLUSIONS: Interleukin-1ß and interferon-γ might effect the formation of thoracic aortic dissection and ascending thoracic aortic aneurysms possibly through the up-regulation of matrix metalloproteinase-9 and the apoptosis of media cells in humans.

[Fibrin glue embolization treating intra-operative type I endoleak of endovascular repair of abdominal aortic aneurysm: long-term result].

OBJECTIVES: To analyze the long-term results of fibrin glue embolization to eliminate type I endoleaks after endovascular aneurysm repair (EVAR), and to assess the feasibility and durability of this technique. METHODS: From August 2002 to June 2010, among the 953 EVAR patients, 51 (5.4%) patients underwent intraoperative transcatheter fibrin glue sac embolization to resolve type I endoleak persisting after initial intraoperative maneuvers to close the leak or in necks too short or angulated for cuff placement. Computed tomographic angiography was performed to assess the outcome after 3, 6, and 12 months and annually thereafter. A retrospective study was conducted, and characteristics of the patients, intra-sac pressure, hospital course, and long-term outcomes were recorded. RESULTS: Among the 51 patients, 19 (37.3%) patients had proximal necks long < 10 mm, and 6 (11.8%) patients had proximal neck angulation > 60°; 22 patients (3 additional iliac extension, 14 cuffs, and/or 8 stents) had been placed with additional devices. After fibrin glue injection, 50 (98.0%) of the 51 endoleaks were successfully resolved, and intra-sac pressure (including systolic, diastolic, mean pressures, pulse pressure, and the mean pressure indexes) decreased significantly in these cases. The patient who failed embolotherapy was converted to open surgery (2.0%); he died 2 months later from multiorgan failure. And other two (4.8%) patients died in the peri-operative period from myocardial infarction. The median of follow-up of 48 patients was 45 months (range 4 - 106 months). The mean maximal aneurysm diameter fell from the baseline (61.5 ± 15.2) mm to (48.8 ± 10.1) mm (P = 0.000). Three (6.2%) patients died in the follow-up duration (1 aneurysm-related, died of renal failure which was caused by the compromised renal artery). Cumulative survival was 97.9% at 1 year, 94.5% at 3 years, and 90.8% at 4 years. No recurrent type I endoleak or glue-related complications were observed in follow-up. CONCLUSIONS: Fibrin glue embolization to eliminate type I endoleak after EVAR has yielded promising results in this study, and it can effectively and durable resolve the type I endoleaks. Balloon occlusion of the inflow of the endoleak must be done during glue injection, to enhance the safety and facilitate formation of a structured fibrin clot.

[Aortorenal bypass with autologous saphenous vein in Takayasu arteritis-induced renal artery stenosis: an analysis of 33 cases].

OBJECTIVE: To clarify the outcome of surgical reconstruction for renal artery in Takayasu arteritis-induced renal artery stenosis (TARAS). METHODS: A retrospective chart review was conducted on 33 consecutive patients with TARAS, who underwent aortorenal bypass (ARB) with autologous saphenous vein graft. There were 9 male and 24 female patients, with a mean age of (25 ± 11) years. The effects on blood pressure and renal function were analyzed. Primary, primary assisted, and secondary patency rates were determined. The effects of various factors on primary patency rate were analyzed. All patients showed hypertension. The mean blood pressure was (175 ± 26)/(100 ± 19) mmHg (1 mmHg = 0.133 kPa). The mean antihypertensive dosage was (2.1 ± 0.6) defined daily dose (DDD). Seventeen patients showed intractable hypertension. Mean estimated glomerular filtration rate was (78 ± 5) ml/min. One patient was dialysis-dependent, and 3 patients were combined with congestive heart failure. RESULTS: ARB was performed for the 39 renal arteries, including 27 unilateral and 6 bilateral bypasses. Postoperative morbidity was 15.2%. All patients survived. During follow-up of mean (56 ± 18) months, two graft occlusions and four graft restenoses occurred. All graft restenoses were eliminated successfully with percutaneous angioplasty, but one patient experienced restenosis again six months later. At 1, 3, and 5 years of follow-up, primary patency was 92%, 89%, and 79%, respectively, primary assisted patency was 95%, 95%, and 91%, respectively, and secondary patency was 95%, 95%, and 91%, respectively. ARB resulted in a decrease in mean blood pressure to 139/85 mmHg (one month post-ARB, P = 0.000) and 136/80 mmHg (last follow-up, P = 0.000), and a reduction in mean antihypertensive dosage to 1.4 DDD (one month post-ARB, P = 0.084) and 0.6 DDD (last follow-up, P = 0.000). Mean estimated glomerular filtration rate increased to 82 ml/min (P = 0.458) one month post-ARB, and 91 ml/min (P = 0.044) at last follow-up, respectively. The dialysis-dependent patient no longer required hemodialysis, and left ventricular dysfunction resolved in all of the three patients. CONCLUSION: ARB using the autologous saphenous vein graft is safe, effective and durable for treating TARAS.

[Effect of the size of abdominal aortic aneurysm on endovascular exclusion and its results].

OBJECTIVE: To evaluate the effect of the diameter of abdominal aortic aneurysm (AAA) on endovascular exclusion (EVE) and its results. METHODS: From March 1997 to June 2007, 429 AAA patients were treated with endovascular stent-graft exclusion. According to the maximal diameter of abdominal aortic aneurysm, the patients were divided into two groups: group A (diameter < 55 mm, n = 274) and group B (diameter > or = 55 mm, n = 155). The diameter of AAA, involvement of iliac artery, length, diameter and distortion of aneurismal neck in the two groups were recorded and compared retrospectively. RESULTS: Patients in group B were significantly older than group A (73.7 vs 71.1 years, P < 0.05). More patients in group B was complicated with coronary artery disease than those in group A (P < 0.05). The mean diameter of AAA in group A was (46.6 +/- 6.8) mm, and (66.8 +/- 11.2) mm in group B (P < 0.05). Proximal aneurysmal necks were shorter, wider and more tortuous in group B than those in group A (P < 0.05). Extraperitoneal approach, embolism of inner iliac artery and reconstruction of another inner iliac artery and stretch technique were more applied in group B. There were more endoleak during operation in group B and more stent-grafts were used. There was significant difference in morbidity rate between the two groups, while no statistic difference in mortality. And in group B, there were a high rate of endoleak and secondary intervention post operation. CONCLUSIONS: The diameter of AAA affects EVE and its results. In small aneurysms, EVE carries better outcome than in big aneurysms.

Simultaneous multi-tear exclusion: an optimal strategy for type B thoracic aortic dissection initially proved by a single center's 8 years experience.

BACKGROUND: Endovascular stent-grafting is widely used to treat thoracic aortic dissection. However, little information is available regarding outcome following simultaneous exclusion of multiple tears. This report details eight years of experience using simultaneous multi-tear exclusion for treatment of Stanford type B thoracic aortic dissection resulting in successful aortic remodeling without adverse events. METHODS: From September 1998 to January 2006, 29 type B thoracic aortic dissection patients (24 men, 5 women; 27 chronic, 2 acute; mean age 58 years, range 45 - 77 years) were treated by simultaneous multi-tear exclusion in our center. Magnetic resonance angiography was used as the preoperative evaluation method. Different kinds of stent-grafts were used. The patients were followed up with contrast-enhanced spiral computed tomography at 6 months postoperatively and yearly thereafter. RESULTS: Twenty-nine surgeries were completed successfully using at least 2 stent-grafts per patient (range: 2 - 6, mean: 2.7). No major procedure-related complications, such as rupture, paraplegia, aortic branch ischemia or cerebral infarction, were observed. During follow-up, favorable remodeling of the aorta was observed. CONCLUSIONS: The mid-term result of thoracic aortic dissection with simultaneous multi-tear exclusion was satisfactory. With the improvement of stent-grafts, simultaneous multi-tear exclusion should find wider application and become an optimal strategy for thoracic aortic dissection.

[Endovascular exclusion of juxtarenal abdominal aortic aneurysm with one-piece customized fenestrated endovascular stent-graft].

OBJECTIVE: To evaluate the technical feasibility of juxtarenal abdominal aortic aneurysm (AAA) repair with fenestrated endovascular stent-graft METHODS: A 64-year-old male was diagnosed with juxtarenal AAA with severe coronary artery stenosis, fenestrations was customized according to precise helical CT data to accommodate visceral and renal arteries. Under general anesthesia and dynamic supervision of digital subtraction angiography (DSA), juxtarenal AAA was excluded with the customized fenestrated stent-graft and balloon expandable mini stent-grafts were deployed into bilateral renal arteries respectively. RESULTS: After operation, DSA showed the patency of the super mesenteric artery, bilateral renal arteries and left hypogastric artery, no endoleak was found. The serum creatinine decreased slightly after operation. CT angiography revealed favorable morphology of the stent-graft without tortuosity, migration, disjoint and endoleak 10 days after the operation and patency of super mesenteric artery, bilateral renal arteries and left hypogastric artery. CONCLUSIONS: The placement of customized fenestrated endovascular stent-graft is a feasible option for juxtarenal AAA.

Role of nitric oxide and inducible nitric oxide synthase in human abdominal aortic aneurysms: a preliminary study.

BACKGROUND: Nitric oxide (NO) is an important mediator in the pathophysiology of many vascular diseases. However, the definite role of NO in human abdominal aortic aneurysm (AAA) formation is unclear. The aim of this study was to investigate production of NO and expression of inducible nitric oxide synthase (iNOS), and their possible role in AAA. METHODS: A total of 28 patients with AAA, 10 healthy controls, and 8 patients with arterial occlusive disease were enrolled into this study. Standard colorimetric assay was used to examine NO concentration in plasma from patients with AAA and normal controls, and in cultured smooth muscle cells (SMCs). Expression of iNOS in aortas and cultured SMCs were detected by immunochemistry. The correlation of iNOS expression with age of the patient, size of aneurysm, and degree of inflammation was also investigated by Cochran-Mantel-Haenszel chi2 test and Kendall' Tau correlation. RESULTS: Expression of iNOS increased significantly in the wall of aneurism in the patients with AAA compared to the healthy controls (P < 0.05) and the patients with occlusive arteries (P < 0.05). iNOS protein and media NOx (nitrite + nitrate) also increased in cultured SMCs from human AAA (n = 4, P < 0.05), while plasma NOx decreased in patients with AAA (n = 25) compared to the healthy controls (n = 20). There was a positive correlation between iNOS protein and degree of inflammation in aneurismal wall (Kendall coefficient = 0.5032, P = 0.0029). CONCLUSIONS: SMCs and inflammatory cells were main cellular sources of increased iNOS in AAA, and NO may play a part in pathogenesis in AAA through inflammation.

[To resolve the difficulties of entering into the aortic dissections' true lumen in endovascular graft exclusion].

OBJECTIVE: To review the methods about resolving the difficulties of entering into the aortic dissections' true lumen in endovascular graft exclusion. METHODS: The patients who had Stanford B type thoracic aortic dissection and been treated with endovascular graft exclusion from September 1998 to February 2004 were reviewed. The operations performed under DSA surveillance. In the operation, the wire was difficult to enter into the true lumen of the aortic dissection in 28 cases, and was wrong into the false lumen then into the true lumen in 4 cases. Five methods were used to resolve these problems, including catheter smoking technique, different position projection, left brachial artery puncture proximal guide-wire floating technique, arterial choice of entering into the true lumen and guide-wire transfixion between proximal and distal. RESULTS: The method of catheter smoking technique was used in 32 cases, different position projection in 12 cases, left brachial artery puncture proximal guide-wire floating technique in 10 cases, arterial choice of entering into the true lumen in 28 cases, and guide-wire transfixion between proximal and distal in 2 cases. The wires were ultimately successful to enter the true lumen and the stent-grafts excluded successfully the tears of the aortic dissections in 32 cases. CONCLUSION: The difficulty of entering into the true lumen and the wrong way into the false lumen could lead to losing the operation, even a disaster. The problem could be resolved by some methods of endovascular techniques.

[Endovascular stent-graft exclusion for Stanford B type aortic dissections: a report of 146 patients].

OBJECTIVE: To assess the operation indications, preoperative evaluation, technique essentials and clinical prospect of endovascular stent-graft exclusion for aortic dissection. METHODS: From September 1998 to April 2003, endovascular stent-graft exclusion for aortic dissection (Stanford B) was preformed in 146 patients. CTA or MRA were used as preoperative evaluation methods. Graft was constructed from self-expanding Z-stents covered with a woven Dacron polyester fabric graft (Talent). The stent-grafts were inserted from the femoral or iliac artery to exclude the tear of dissection, and all operations were performed under DSA guidance. RESULTS: The grafts were installed successfully in 145 patients. In 119 patients only proximal tears were excluded, and 26 patients who had both the proximal and distal tears were excluded. The mean follow-up period was 16 months (1 - 54 months). Six patients died within the perioperative period, 2 patients died during the follow-up, 2 patients had recurrence of aortic dissection (Stanford A) and cured by Bentall operation. The others were in good state. No accidents related to the dissection and operation occurred. CONCLUSIONS: Endovascular graft exclusion may be a safe and effective treatment for selected patients with thoracic aortic dissection. Endoleak may lead to aneurysmal expansion and rupture. Further follow-up is necessary to evaluate its long-term effect.