Songqi Li

MCP-1 Stimulates MMP-9 Expression via ERK 1/2 and p38 MAPK Signaling Pathways in Human Aortic Smooth Muscle Cells

Objective: We investigated the molecular mechanism underlying the role of monocyte chemoattractant protein-1 (MCP-1) in the formation and development of human abdominal aortic aneurysm (AAA). Methods: We examined protein expression profiles using a protein array and found that MCP-1 was the most highly expressed protein in AAA tissues compared with normal aortas. To investigate the potential mechanism of MCP-1 involvement in the pathogenesis of AAA, we treated human aortic smooth muscle cells (HASMCs) with human recombinant MCP-1. Results: MCP-1 was the most highly expressed protein in AAA tissues compared with normal aorta; matrix metalloproteinase-9 (MMP-9) expression was also significantly increased. Treatment with MCP-1 significantly increased the expression and activation of MMP-9 and activated the three major mitogen activated protein kinases (MAPKs) extracellular signal regulated kinase (ERK), c-Jun amino terminal kinase (JNK1/2) and p38 MAPK. Furthermore, MCP-1-induced secretion of MMP-9 was inhibited by U0126 (inhibitor of the ERK 1/2 pathway) and SB203580 (inhibitor of the p38 MAPK pathway), but not SP600125 (inhibitor of the JNK1/2 pathway). Conclusion: These data demonstrate that MCP-1 stimulates secretion of MMP-9 directly through the ERK1/2 and p38 MAPK mediated pathways in HASMCs. Thus, inhibition of this molecular mechanism might be a potential therapeutic target in the non-surgical treatment of AAA.

Endovascular Stent-graft Treatment for Stanford Type A Aortic Dissection

OBJECTIVE The aim of the study is to summarise our experience of endovascular stent grafting for Stanford type A aortic dissection. DESIGN Retrospective analysis at single centre. METHODS From January 2001 to January 2009, we treated 45 cases of Stanford type A aortic dissection with endovascular stent grafting. The entry tear was located at the ascending aorta in 10 cases (DeBakey type I), the aortic arch in 14 cases and the distal aortic arch or proximal descending aorta in 21 cases in which the ascending aorta was also involved by the dissection. RESULTS The surgical success rate was 97.8% (44/45) and 30-day mortality rate was 6.7% (3/45). Type I endoleaks occurred in 10 cases: one patient died intra-operatively, four were successfully treated with ballooning, four were sealed with aortic cuffs and one case caused by left subclavian artery (LSA) reflux was sealed with an occluder. Average follow-up time was 35.5 ± 5.4 months. Up to the most recent review or death, 32 patients had complete thrombosis and 10 had partial thrombosis inside the false lumen. Two deaths occurred after 30-days postoperatively. CONCLUSION Endovascular stent-graft treatment is a minimally invasive and effective method to treat Stanford type A aortic dissection.

Endovascular treatment of arch and proximal thoracic aortic lesions.

OBJECTIVE To analyze at one institution the endovascular treatment for aortic arch and proximal thoracic aortic lesions, categorize open arch reconstruction, and make preliminary recommendations based on pathology (dissection vs aneurysm), and anatomical extent of disease. METHODS A retrospective review of aortic arch and descending thoracic aortic lesions managed with endovascular treatment between June 2002 and June 2007. RESULTS Thirty-four patients received endovascular repair for aortic dissection (n = 28) and aneurysm (n = 6). Open supra-aortic transposition or debranching of the great vessels was performed in 14 cases of dissection (50%) and six cases (100%) of aneurysm. In 14 dissections, the entry tear was located in the distal aortic arch, enabling the left subclavian artery to be sealed without reconstruction. The procedures were successful in 33 patients (97.1%); one intraoperative death occurred. Type I endoleaks were found intraoperatively in eight cases. After management with balloon angioplasty and by extending the stent implantation, the endoleaks resolved in four cases and decreased in four cases. One patient with Stanford type A dissection died from an unknown cause 3 months after treatment. The overall survival rate was 94.1% (32/34), and all bypass grafts remained patent during the follow-up period. CONCLUSIONS Endovascular stent grafting is a safe and effective method for the treatment of aortic arch lesions. Transposition of the supra-aortic great vessels can be effectively combined with endovascular stent grafting to ensure both cerebral blood supply and enough landing area for the stent graft.

Preoperative angiography and transarterial embolization in the management of carotid body tumor: a single-center, 10-year experience.

BACKGROUND:Sixty percent of paragangliomas are located unilaterally at the carotid bifurcation. These are referred to as carotid body tumors (CBTs). OBJECTIVE:To present our 10-year experience in the management of patients with CBTs, and to evaluate the efficacy of angiography and preoperative embolization technique in this retrospective study. METHODS:Sixty-two patients with surgically removed CBTs (Shamblin class II and III), were divided into two groups. Group I, the preoperative embolization group, included 33 patients with 11 class II lesions and 25 class III lesions. Group II, the group that had surgery only, without preoperative embolization, included 29 patients with 9 class II lesions and 21 class III lesions. Comparisons were made between the groups in terms of mean intraoperative blood loss, mean operation time, mean postoperative hospital stay, and clinical complications. RESULTS:In group I, post-embolization angiography demonstrated complete tumor devascularization in 25 (76%) lesions and partial devascularization in 11 (24%) lesions. All but 1 (2%) lesion were completely excised. Mean intraoperative blood loss, mean operation time, and mean hospital stay were 354.8 ± 334.4 mL, 170.3 ± 75.4 min, 8.0 ± 2.1days in group I and 656.4 ± 497.4 mL, 224.6 ± 114.0 min, 9.5 ± 3.5days in group II, respectively. In group II, 27 lesions (91%) were completely removed. The transient ischemic attack (TIA) and cranial nerve injury incidence rates were 10.3% and 13.8% in group II and only 3% for TIA in group I. CONCLUSION:These results suggest angiography is highly valuable for the diagnosis of CBT. Preoperative selective embolization of CBT is an effective and safe adjunct for surgical resection, especially for Shamblin class II and III tumors.

Somatic mutations in exon 17 of the TEK gene in vascular tumors and vascular malformations

OBJECTIVE As a common disease, the molecular etiology of noninherited vascular anomalies is still poorly understood. Recently, somatic mutations in exon 17 of the endothelial cell tyrosine kinase receptor Tie-2 (encoded by TEK) were identified in 49.1% of patients with common sporadic venous malformation, a subtype of vascular anomalies. We assessed whether such a mutational region also had a role in the Chinese population or in other subtypes of noninherited vascular anomalies (vascular tumors and vascular malformations). METHODS Direct sequencing of polymerase chain reaction (PCR)-amplified DNA, extracted from 139 lesions in 129 individuals with noninherited vascular anomalies (vascular tumors or vascular malformations) and 60 control samples, was used for detecting the mutations in exon 17 of the TEK gene. Mutations were confirmed by allele-specific PCR. Clone sequences were then used for the mutations identified for the first time. We also explored the associations between these mutations and clinical characteristics (gender, onset age, number of lesions, severity, category, and recurrence of the disease) in both vascular tumors and vascular malformations. RESULTS Two somatic TEK mutations (Y897C, R915C) were identified in vascular tumors, and seven somatic TEK mutations (Y897H, Y897C, L914F, R915C, S917I, R918C, R918H) were identified in vascular malformations. Among these mutations, R918C (2,752 C > T) and R918H (2,753 G > A) were first identified in noninherited vascular anomalies. Somatic TEK mutations were detected in lesions from 4 of 23 (17.4%) vascular tumors and 35 of 106 (33.0%) vascular malformations, where most mutations were single substitutions in vascular tumors (100%) and vascular malformations (88.6%), while the remainders were double substitutions. In addition to the reported venous malformation, such mutations were identified in some other subtypes of vascular anomalies, including vascular tumors (infantile hemangioma, pyogenic granuloma, and epithelioid hemangioma) and vascular malformations (capillary malformation, arteriovenous malformation, capillary lymphatic malformation, and capillary arteriovenous malformation). By contrast, these mutations were absent from the control tissues or blood. However, mutations showed no association (P > .05) with clinical characteristics in vascular anomalies or either of its two types (vascular tumors or vascular malformations). CONCLUSIONS Our study revealed that somatic mutations in exon 17 of the TEK gene were more common in noninherited vascular anomalies than previously reported. Furthermore, such substitutions may shed new light on the molecular etiology, diagnosis, and potential therapeutic targets of vascular anomalies.

Tolerable Hemodynamic Changes after Femoral Artery Ligation for the Treatment of Infected Femoral Artery Pseudoaneurysm

BACKGROUND We analyzed the hemodynamic changes induced by femoral artery ligation with concomitant thrombectomy in intravenous drug abusers with infected femoral artery pseudoaneurysm (IFAP) and their clinical significance. METHODS Between January 2000 and November 2007, a total of 55 patients presented to our clinic with IFAP. Among these patients, 54 were treated by femoral artery ligation with concomitant thrombectomy. Open collateral circulations were assessed by intraoperative angiography, including detection of mean artery pressure (MAP) of back-flow from the profunda femoris artery and the superficial femoral artery after operation. Patients were followed up for 3-72 months (mean 35). The data were then subjected to statistical analysis. RESULTS Preoperative death occurred in one patient due to acute onset of drug addiction in the ward. Preoperatively, massive necrosis developed in the left limb of the only patient with bilateral IFAPs. All 54 patients underwent femoral artery ligation with concomitant thrombectomy, including nine cases of ligation of the external iliac artery and one case of above-knee limb amputation. All wounds were completely healed within 3 months. Six late deaths (11.1%), resulting solely from refractory drug addiction, were observed during the follow-up period, of which two occurred 2 years, one 4 years, and three 5 years postoperatively. No toe amputations were noted during the follow-up period. Fourteen patients (25.9%) developed intermittent claudication. One postoperative limb was lost. Of all 54 patients, 38 were subjected to collateral circulation assessment by intraoperative angiography. Collateral circulations were found well open in a baseline path with four stations down to the distal lower limbs of all assessed patients. Four preferred types of iliac-femoral collaterals were defined. Postoperatively, compared to the external iliac artery, the MAP levels of back-flow from the profunda femoris artery and the superficial femoral artery significantly dropped to 43.89+/-2.75 and 18.08+/-2.76 mm Hg, respectively. CONCLUSION As a result of femoral artery ligation without reconstruction, well open collateral circulations and acceptable distal arterial runoff blood are seen, which suggests that this procedure is a reliable alternative to the emergent treatment of IFAPs in drug addicts. However, arterial reconstruction may be used as a backup approach if necessary during observation.

Endovascular Stent-Graft Repair of Aortic Dissection

Between October 2000 and January 2002, 9 consecutive male patients with subacute or chronic aortic dissection underwent stent-graft placement. The indication for surgery was continuous pain or aneurysm development. One patient had a type A dissecting aortic aneurysm with a primary tear in the ascending thoracic aorta; the other 8 had type B dissection. Placement of an endovascular stent-graft was technically successful in 8 patients, and one underwent an open procedure for abdominal aortic fenestration. The entry site was sealed and the false lumen disappeared in 8 cases, and thrombosis of the false lumen was obtained. Rupture of an iliac artery dissecting aneurysm occurred in one patient 2 days after stent-graft placement; abdominal aortic fenestration with prosthetic replacement of the distal abdominal aorta was performed. One patient died of myocardial infarction 3 days after the stent-graft procedure. During a mean follow-up period of 7 months (1–16 months), one patient died of acute myocardial infarction at 11 months. It was concluded on the basis of these short-term results that endovascular repair of aortic dissection is a promising treatment, and abdominal aortic fenestration is a useful adjuvant procedure.

The value of endografts in the surgical management of arterial lesions secondary to Behçet disease

Background: This study summarizes our experience in the surgical management of arterial lesions secondary to Behçet disease (BD) and assesses the value of endografts. Methods: Data from BD patients with arterial lesions managed surgically in our center from January 1998 to December 2015 were studied retrospectively. Surgical procedures, graft selection, graft‐related complications, and retreatments were analyzed. Results: We recruited 33 patients (29 men and 4 women; male‐to‐female ratio, 7.25:1) with an average age of 36.7 years (range, 25‐51 years). The arterial lesions included 27 aneurysms in 24 patients and nine stenotic or occlusive lesions in nine patients. Immunosuppressive therapy was administered routinely preoperatively and postoperatively as recommended. Altogether, 15 great saphenous veins (GSVs), 8 synthetic grafts, and 13 endografts were used in 36 primary procedures. The mean follow‐up duration was 3.8 ± 2.9 years. Graft‐related pseudoaneurysm was seen in three GSVs (20%) and in three synthetic grafts (38%) at the anastomosis, but not in endograft implantations (log‐rank, P = .171). Graft occlusions were observed in 1 GSV (7%), 2 synthetic (25%), and 2 endografts (15%; log‐rank, P = .881). Graft infection occurred in one synthetic graft (13%) and in one endograft (8%) but not in the GSVs (log‐rank, P = .689). Graft‐related artery rupture occurred in only one endograft (8%). Two patients died, giving a mortality rate of 6.1%. Conclusions: In the surgical management of arterial lesions secondary to BD, endografts were superior to GSV and synthetic grafts in decreasing anastomotic pseudoaneurysm. However, improvements are needed to enhance the long‐term patency and reduce infections.