Matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) play a complex role in the pathogenesis of atherosclerosis. We compared (1) the histopathological findings in patients with abdominal aortic aneurysms (AAA) and aortoiliac occlusive disease (AOD); (2) the expression of MMP-2/MMP-9 and TIMP-1/TIMP-2 in aortic layers, inflammatory cells and smooth muscle cells (SMCs), aiming to identify the common underlying pathogenic mechanisms of the disease development. Samples were obtained from 30 patients with AAA and 30 with AOD. Aortic histology and immunohistochemistry were performed to evaluate inflammatory changes and MMP and TIMP expression. Thrombosis and ulceration were more frequent in AOD than in AAA. The MMP-9 expression was elevated in all aortic layers of AAA patients and in media/adventitia of AOD patients, mainly followed by lower expression of its inhibitor TIMP-1. Higher MMP-9 expression was also found in SMCs and macrophages of both AAA and AOD specimens, while higher TIMP-1/TIMP-2 were predominantly observed in the lymphocytes and macrophages of the aneurysm. These results showed that both conditions exhibited increased MMP-9 expression; however, the MMP expression pattern differed to some degree between the aneurysms and occlusive disease. The variations in molecular mechanisms underlying dilatative/stenosing disease warrant further investigation.
- MeSH
- aneurysma břišní aorty metabolismus MeSH
- arteriální okluzní nemoci metabolismus MeSH
- imunohistochemie MeSH
- lidé MeSH
- matrixová metaloproteinasa 9 metabolismus MeSH
- matrixové metaloproteinasy metabolismus MeSH
- myocyty hladké svaloviny metabolismus MeSH
- nemoci aorty metabolismus MeSH
- tkáňový inhibitor metaloproteinasy 1 metabolismus MeSH
- tkáňový inhibitor metaloproteinasy 2 metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
The limitations of surgical revascularisation and pharmacological treatment in peripheral arterial occlusive disease (PAOD) are well recognized. Therapeutic options for critical leg ischemia are consequently limited to percutaneous transluminal angioplasty (PTA) or surgical revascularisation. Unfortunately, many patients with critical leg ischemia are poor candidates for either procedure. Therapeutic angiogenesis is a novel promising tool to treat these patients. Experimental and clinical and trials of gene transfer for therapeutic angiogenesis have already shown some clinical efficacy. This review is focused on gene transfer techniques in preclinical and clinical therapeutic angiogenesis, angiogenic growth factors, vectors, delivery methods and routes. The results of clinical and experimental studies, safety and side effects of gene therapy, and the perspectives of future research are also discussed.
- MeSH
- arteriální okluzní nemoci metabolismus terapie MeSH
- dolní končetina krevní zásobení MeSH
- endoteliální buňky metabolismus transplantace MeSH
- financování organizované MeSH
- fyziologická neovaskularizace MeSH
- genetická terapie trendy MeSH
- genetické vektory MeSH
- ischemie metabolismus terapie MeSH
- klinické zkoušky jako téma MeSH
- lidé MeSH
- modely u zvířat MeSH
- technika přenosu genů MeSH
- vaskulární endoteliální růstové faktory genetika metabolismus MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- přehledy MeSH
