Akimasa Yamashita

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.

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.

Experimental and Clinical Studies Investigating the Efficacy of Distal Anastomosis with Patch Plasty in Bypass Operations with Expanded Polytetrafluoroethylene Grafts

Abstract.Purpose: We investigated the efficiency of distal anastomosis with patch plasty (DAPP), both experimentally and clinically. Methods: In our experimental study, dogs were divided into two groups: a control group in which anastomosis was performed without DAPP (n = 7), and a DAPP group in which DAPP was performed at the distal anastomosis (n = 7). In our clinical study, 169 femoropopliteal bypasses were divided into three groups and analyzed. In one group, the saphenous vein was used (SVG group, n = 65); in one group, an expanded polytetrafluoroethylene (ePTFE) graft was used without DAPP (ePTFE group, n = 64); and in one group, an ePTFE graft was used with DAPP (DAPP group, n = 40). Results: In the experimental study, the ratio between the area of thrombus adherence and the entire area of the intraluminal surface of the graft, defined as the thrombus covering ratio, was 48.9% in the control group and 30.2% in the DAPP group. The ratio in the DAPP group was significantly lower than that in the control group. In the clinical study, although there were no significant differences among the three groups in cumulative patency rates of the femoral above-knee popliteal arterial bypasses, the patency in the DAPP group was excellent. The cumulative patency rates of the femoral below-knee popliteal arterial bypasses in the ePTFE group were significantly lower than those in the other two groups. Conclusion: There results suggest that the addition of DAPP may achieve excellent graft patency.

Pulmonary and Deep Vein Thrombosis in a Young Patient with Protein S Deficiency: Report of a Case

A 27-year-old man, who was diagnosed as having familial protein S deficiency, developed deep vein thrombosis complicated with pulmonary thromboembolism. Anticoagulant therapy and thrombolytic therapy were commenced after the insertion of a temporary inferior vena cava filter (t-IVC-f). However, on day 5 after t-IVC-f insertion, IVC venography showed filter thrombosis. On day 13, we made a venotomy and removed the captured thrombi and inserted a permanent IVC-f. After removal of the t-IVC-f via the right brachial vein, thrombi that had not been seen earlier appeared in the right atrium (RA). It was suspected that the thrombi around the catheter had likely been stripped off during the catheter removal procedure. After the abdomen was closed, an extra operation was immediately performed. Under complete extracorporeal circulation, the RA was opened and the all thrombi were removed. The patient recovered well and was discharged on the 21st postoperative day without any complications.