Kentaro Fujioka

Enhanced Expression of Matrix Metalloproteinase-9 in Abdominal Aortic Aneurysms

Abstract. Abdominal aortic aneurysms (AAAs) are characterized by structural alterations of the aortic wall resulting from degradation of collagen and elastin. Matrix metalloproteinases (MMPs), particularly MMP-2 and MMP-9, show strong elastinolytic activity. We examined the levels of mRNA for MMP-2, MMP-9, membrane type (MT)-MMP-1, tissue inhibitor of metalloproteinase-1 (TIMP-1), and TIMP-2 in AAAs (n= 8), atherosclerotic occlusive diseases (AOD) (n= 8), and normal subjects (n= 8) using the reverse transcription-polymerase chain reaction (RT-PCR). We also analyzed the gelatinolytic activity of these metalloproteinases using gelatin zymography. The levels of MMP-2 and MMP-9 mRNA were increased in the AAA group compared with those in the AOD group and normal subjects. The levels for TIMP-1 and TIMP-2 mRNA in the AAA group were also higher than those in the AOD and normal groups. Only in the case of MT-MMP-1 was the difference between AAA and AOD not statistically significant. By gelatin zymography with the same samples used for RT-PCR, gelatinolytic activity of MMP-9 was elevated in all AAA tissues. The 62-kDa form of MMP-2 was elevated in both the AAA and AOD groups and did not differ significantly between them. Linear regression analysis demonstrated a significant positive correlation between mRNA levels of MMPs and those of TIMPs. These observations suggest that aneurysm formation in patients with atherosclerosis is related to the degree of MMP-9 expression.

Is endovascular treatment of abdominal aortic aneurysms less invasive regarding the biological responses

To compare the biological responses following an endoluminal repair and a conventional open repair of abdominal aortic aneurysm (AAA), 14 patients who underwent an endoluminal repair (endograft group) and 26 who underwent an open repair (open group) were investigated. As markers of biological responses, interleukin-6 (IL-6) and -8 (IL-8), granulocyte elastase (GEL), white blood cell count (WBC), and serum C-reactive protein (CRP) were all measured preoperatively as well as on postoperative days (POD) 1, 3, and 6. In addition, the blood loss, duration of surgery, initial oral intake the day after surgery, and length of hospital stay were compared between both groups. The plasma levels of IL-6, GEL, CRP, and WBC were higher in the endograft group than in the open group, while the CRP, WBC, and GEL levels all peaked on POD 3. The plasma level of IL-6 remained high in the endograft group, compared with that in the open group throughout the study period. Conversely, blood loss, initial oral intake the day after surgery, and the length of hospital stay were all significantly greater in the open group than in the endograft group, although there was no significant difference in the duration of surgery between the two groups. These findings indicate that although the endoluminal repair of AAA is supposed to be less invasive, the biological responses tend to be greater because of the manipulation related to the insertion of the stent graft.

Matrix Metalloproteinase Expressions in Arteriosclerotic Aneurysmal Disease

Medial degeneration of extracellular matrix (ECM) proteins in the wall of abdominal aortas results in smooth muscle cell destruction, a loss of architectural integrity, and abdominal aortic aneurysm (AAA) formation. It has been theorized that an imbalance between proteinases and their naturally occurring inhibitors is the cause of these observed histologic abnormalities. Therefore, the purpose of this investigation was to determine if differences in the matrix metalloproteinase (MMP) -2 and -9, tissue inhibitor of metalloproteinase-1 (TIMP-1), tissue-type plasminogen activator (tPA), and urokinase-type plasminogen activator (uPA) protein and activity levels existed between infrarenal AAA and normal abdominal aortic tissue specimens. Between November 1995 and January 1997, 10 patients undergoing elective infrarenal AAA repair had a portion of their aneurysm walls snap frozen in liquid nitrogen and processed for subsequent western blot or zymographic analysis. Tissue specimens from 6 normal abdominal aortas obtained from fresh cadaver specimens were similarly processed and served as controls. Protein levels for MMP-2, MMP-9, TIMP-1, uPA, and tPA were analyzed by western blotting. The degree of MMP-2 and MMP-9 gelatinolytic activity was analyzed by zymography. Detection and immunolocalization for MMP-2, MMP-9 and CD68 was performed on tissue sections of AAA and normal infrarenal abdominal aortas fixed in 10% formalin. MMP-9 and tPA protein levels were increased in AAAs compared to controls by western blotting. However, uPA levels were slightly increased in controls. No differences in TIMP-1 protein levels were identified. Similarly, zymography demonstrated increased MMP-2 and MMP-9 gelatinolytic activity in AAAs compared to controls (p<0.05). CD68-positive cells (macrophages) in the adventitia and media demonstrated immunoreactivity to MMP-9. This investigation demonstrated increased MMP-9 proteinase activity and tPA protein levels in the walls of AAAs, as well as inflammatory leukocyte invasion of the adventitia and media compared to controls. These data suggest that leukocyte-derived MMP-9 is associated with aortic wall degeneration and aneurysm formation. Furthermore, activation of MMP-9 may be caused by increased tPA levels in the walls of AAAs.

Fatal Diffuse Atheromatous Embolization Following Endovascular Grafting for an Abdominal Aortic Aneurysm : Report of a Case

Abstract A 78-year-old woman with an abdominal aortic aneurysm, 57 mm in diameter, was admitted to our hospital for endovascular grafting. Preoperative computed tomography and angiography showed friable mural thrombus in the suprarenal and infrarenal aorta, and a diagnosis of shaggy aorta was made. Postoperatively, the patient suffered cerebral infarction, and disseminated intravascular coagulopathy with multiple organ failure developed, resulting in early death on the third day after surgery. An autopsy revealed diffuse atheromatous embolization into the celiac, superior mesenteric, bilateral renal, bilateral hypogastric (trash buttock), and peripheral arteries. This case report serves to demonstrate that an abdominal aortic aneurysm with a shaggy aorta in the proximal neck is a contraindication to endovascular grafting, and that predicting the possibility of diffuse atheromatous embolization by detecting a shaggy aorta is the best way to prevent this catastrophic complication.

A Comparison of CORVITA and Expanded Polytetrafluoroethylene Vascular Grafts Implanted in the Abdominal Aortas of Dogs

The utility of CORVITA vascular grafts, composed of an inner layer of meshed polyurethane fibers and an outer layer of meshed Dacron reinforcement, for replacement of the abdominal aorta was assessed in a canine model and compared with expanded polytetrafluoroethylene (ePTFE) grafts. CORVITA or ePTFE vascular grafts were implanted and left in place for 3 or 6 months. After removal, they were inspected macroscopically and histologically. Microspectrophotometry was used to quantify smooth muscle cells (SMCs), elastin (EL), and collagen (CL) in the media of the native artery. The patency rate of the CORVITA grafts after 6 months was 100%, whereas that of the ePTFE grafts was only 50%. Moreover, stenoses were apparent in all of the ePTFE grafts, but in only 43% of the CORVITA grafts. The intimal thickness at the distal anastomosis was significantly greater at 3 months in the ePTFE grafts (P<0.01), and there were significantly more SMCs in the host arterial media at the proximal and distal anastomoses in these grafts. Thus, better long-term patency can be expected with CORVITA grafts than with ePTFE grafts. This conferred advantage is most likely attributable to the less pronounced intimal hyperplasia which results from the proliferation of SMCs in the media of the native artery.

DETECTION OF TYPE III COLLAGEN FRAGMENTS IN SPECIMENS OF ABDOMINAL AORTIC ANEURYSMS

The purpose of this study was to analyze the collagens in aortic aneurysm walls and to investigate the mechanism of the formation of calcified abdominal aortic aneurysms (AAAs). Collagens were extracted from human aneurysmal aortic walls obtained during surgery, and from human nonaneurysmal aortic walls obtained at autopsy, using pepsinacetic acid digestion. Electrophoresis and immunoblotting were performed. Type III collagen was found to be reduced in the arteriosclerotic aneurysmal aortic walls. The α1 chain of type III collagen/α1 chain of type I collagen ratio was 0.35 ±0.11 in the aortic aneurysms and 0.68 ± 0.11 in the nonaneurysmal aortic walls (P=0.0111). All the calcified aneurysms were associated with type III collagen fragments having molecular mass of approximately 70 kDa and 30 kDa as estimated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Thus, we concluded that AAAs with calcification may be caused by an abnormal degradation of type III collagen.

Successful management of a giant spinal arteriovenous malformation with multiple communications between primitive arterial and venous structures by embolization: Report of a case

A 47-year-old woman was admitted to our hospital with a giant spinal arteriovenous malformation (AVM) causing heart failure and thoracic myelopathy. Angiography revealed that the spinal AVM had multiple feeding vessels branching from the 5th through 12th intercostal arteries. The drainage vein flowed to the azygos vein and superior vena cava. The AVM destroyed the 7th thoracic vertebra. The cardiac output was 16.7l/min and the shunt ratio was 64% before treatment. Embolization with cyanoacrylate was performed because the operation was considered to be associated with a significant risk of paraplegia and organ ischemia. The cardiac output decreased to 11.6l/min and the shunt ratio was reduced to 32%. After embolization the patient demonstrated no symptoms of either heart failure or sensory deficits. During embolization, provocative tests using sodium amytal and lidocaine with magnetic stimulation were also performed. The above findings suggest that provocative tests and magnetic stimulation are useful to predict paraplegia, which could result from embolization while, in addition, embolization is considered to be a useful treatment for multiple shunt and nidus in this region.

Klippel-Trenaunay syndrome associated with splenomegaly: report of a case.

We report herein the case of a 19-year-old woman, diagnosed as having Klippel-Trenaunay syndrome at the age of 3 years, who presented to our hospital with severe abdominal pain. Abdominal computed tomography revealed splenomegaly, ascites, and paracentesis confirming an intrabdominal hemorrhage. Thus, an emergency laparatomy was performed for a suspected splenic rupture, and 2.5L of blood was drained from the abdominal cavity. Splenomegaly was confirmed, and a splenectomy was performed. The patients postoperative course was complicated by disseminated intravascular coagulation, but she recovered and was discharged 3 weeks following surgery. Pathological examination of the spleen suggested that the splenomegaly was caused by high venous pressure due to splenic vein stenosis. To our knowledge, this is the first reported case of Klippel-Trenaunay syndrome associated with marked splenomegaly.

Arterial Reconstruction: Justified for Patients with Intermittent Claudication?

Abstract. The objective of this study was to evaluate the effects of arterial reconstruction in patients with intermittent claudication. A total of 243 patients (305 limbs) underwent lower extremity vascular reconstruction at our institution from 1979 to 1995. They were assessed by physical examination, pulse volume recordings, segmental pressure, Duplex ultrasonography, and intravenous subtraction arteriography to evaluate the effects of arterial reconstruction. Surviving patients (220 limbs) were enrolled for evaluation of outcome during the follow-up period. There were 59 deaths during the follow-up period. The cumulative life-table 5-year patency rates were 90% ± 3%, 73% ± 6%, and 74% ± 10% for aortoiliac, infrainguinal, and aortofemorodistal arterial reconstructions, respectively. Among 129 repairs in the aortoiliac region, Fontaine stages I, II, and III were found in 109 limbs (84.5%), 17 limbs (13.2%), and 2 limbs (1.5%), respectively. There was one (0.7%) minor amputation. There was Fontaine stage I in 50 limbs (76.9%), Fontaine stage II in 14 limbs (21.5%), and Fontaine stage III in 1 limb (1.5%) for repairs in the infrainguinal region. Among the 26 aortofemorodistal repairs, there was Fontaine stage I in 21 limbs (81%) and Fontaine stage II in 5 limbs (19%). There was a statistically significantly higher incidence of Fontaine stage I than Fontaine stage II or III in aortofemoral, infrainguinal, and aortofemorodistal arterial reconstructions (p < 0.0001). Arterial reconstruction for patients at Fontaine stage II offered benefits and improved quality of life at follow-up. Arterial reconstruction for patients at Fontaine stage II offers benefits and improved quality of life at follow-up. It was concluded that the significant improvement in quality of life after arterial reconstruction warrants continued use of the procedure in patients with intermittent claudication.

The lack of type III collagen in a patient with aneurysms and an aortic dissection

We analyzed 79 consecutive patients with aneurysms and found a patient who lacked type III collagen. Collagen was extracted from the skin, and the lack of type III collagen was determined by means of sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Only 1 of the 79 patients was found to lack type III collagen. This patient was a 55-year-old man who had sustained an abdominal aortic aneurysm and aortic dissection. He did not show any of the typical clinical symptoms of Ehlers-Danlos syndrome type IV, such as hyperextensible skin and joints. He had none of the usual risk factors nor any clear family history of the syndrome. Furthermore, his collagen fibrils demonstrated a homogeneous appearance. This case may represent a new form of type III collagen deficiency.