| ObjectiveThe recent interest in developing new therapeutic strategies for patients with small asymptomatic AAAs has led to greater efforts to investigate and define the cellular and molecular nature underlying mechanism of aneurysmal degeneration. Previous studies showed that multiple factors are responsible for the patho-genesis of this disease. Among these factors, mechanical failure of elastin and collagen is a fundamental cause of AAAs, which is considered to be the result of increased level of Matrix Metalloprotainase (MMPs) , the Matrix ( elastin and collagen) -degrading enzymes in the aortic wall. Inflammatory infiltration is an important feature of AAAs and has been well documented. Inflammatory cells, predominantly macrophages and lymphocytes, infiltrating through the aortic media and adventitia, have been reported to play a significant role in the destruction of elastin and collagen by directly secreting MMPs. AAAs have been shown to display increased apoptosis of SMCs, which are generally predominant cell types in aortic media and contribute substantially to the elastic lamellar architecture of the vascular wall.In addition to these pathophysiological factors, recent studies shifted their interest to the role of NO in the development of AAA in an attempt to further understanding of molecular pathogenesis of this disease. NO is derived from the oxidation of L - arginine catalyzed by Nitric Oxide Synthase ( NOS). In blood vessels NOS exists mainly as a family of related but distinct isoforms, including en-dothelial (eNOS) and inducible (iNOS) isoforms. NO produced by eNOS in the endothelial cells is present at relatively low levels, and is considered to take a vasoprotective role. In contrast, iNOS is widely distributed in a variety of celltypes and upon induction can produce a high output of NO. Thus, excessive NO generation is important not only for its local destructive effect to extracellular matrix (ECM) and cytotoxic effect to host cells, but also for the regulation of cell growth and programmed cell death ( apoptosis).Recent studies show that AAA tissue contains a significantly elevated concentration of nitrite ion, which is destructive of elastic fibers. Research with animal model shows that inhibition of iNOS limits nitric oxide production and aneu-rysm expansion. Transfection of vascular SMCs using iNOS cDNA showed that generation of NO derived from iNOS overexpression led to a marked apoptosis of vascular SMCs. In addition, the drugs shown to limit the AAA expansion or inhibit MMPs in recent experimental or clinical studies are known to inhibit NO production. These suggest that NO might play an important role in the pathogen-esis of aneurysmal formation. However, expression of iNOS and its sources in human AAA have not been investigated, and previous studies have largely been based on indirect evidence from other vascular diseases. To elucidate this problem and to detect the possible role of NO ( or iNOS) in the pathophysiology of AAA, the present study was undertaken. The aims were to detect expression of iNOS in association with its cellular localization, detect the presence of one end -product of the NO reaction (nitrotyrosine) , and detect the distribution of apoptosis and cross - correlation with iNOS in AAA.MethodsHuman AAA specimens were obtained from patients undergoing elective operation ( n = 25) . The average age of the patients was 69 years ( range 55 to 80 years ). The average size of the aneurysmal lesions estimated by CT scan and/or ultra - sound was 6.7cm (range, 3.8 to 9. 0 cm). Ninety - six percent of the patients were men and four percent women. Normal aortic specimens were obtained from normal organ transplant donors ( n = 10) , the patients had no evidence or medical history of aneurysmal or occlusive disease ( average age 59 years old). Each aneurysmal tissue was divided into two parts; one for frozen, one for paraffin sections for histochemistry or immunohistochemistry and in situhybridization.Formalin - fixed specimen were processed...
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