Molecular targets and abdominal aortic aneurysms.
Molecular targets and abdominal aortic aneurysms.
复制标题
DOI：
10.2174/157489009788452940
复制
发表时间：
2009-05
期刊：
影响因子：
--
通讯作者：
S. Nanda;Shree G. Sharma;S. Longo
中科院分区：
文献类型：
--
作者：
S. Nanda;Shree G. Sharma;S. Longo
腹主动脉瘤(AAA)在美国是一个非常严重的健康问题。目前的治疗选择是手术或血管内支架置入术。药物治疗效果不是很好，也没有药物治疗可以影响AAA的消退。如果药物可以防止或减少50%的小AAA进展率，许多老年患者将没有必要进行手术或血管内干预。基础研究有助于确定AAA发病的分子基础。血管紧张素II、白三烯-LT4、前列腺素-PGE_2、白介素II、肿瘤坏死因子、组织型纤溶酶原激活剂、c-jun氨基末端激酶、核因子-kappaB、Rho激酶、骨保护素和糜乳酶是主动脉损伤的介质。它们协同作用，激活基质金属蛋白酶、丝氨酸蛋白酶和半胱氨酸蛋白酶。其结果是主动脉壁蛋白、细胞外基质的降解和血管平滑肌细胞的凋亡。对致病途径的深入了解导致了大量新分子的研究和开发，这些分子可以抑制这些途径，延缓AAA的扩张。我们讨论了可能在防止AAA进展方面起到有益作用的新的专利制剂。
Abdominal aortic aneurysm (AAA) is a very significant health problem in the United States. Current therapeutic options are surgery or endovascular stenting. Medical treatment is not very effective and there is no medical therapy that can effect the regression of AAA. Surgical or endovascular intervention for many older patients will be unnecessary if medications could prevent or reduce the progression rate of small AAA by 50%. Basic research has helped to determine the molecular basis of pathogenesis in AAA. Mediators of aortic damage include angiotensin II, leukotriene-LT4, prostaglandin- PGE2, interleukins, tumor necrosis factor, tissue plasminogen activator, c-Jun N-terminal Kinase, NF-kappaB, Rho kinases, osteoprotegerin and chymases. They work in concert to activate matrix metalloproteinase, serine proteases and cysteine proteases. The result is degradation of aortic wall proteins, extracellular matrix and apoptosis of vascular smooth muscle cells. An enhanced understanding of the pathogenetic pathways has led to significant research and development of new molecules, which can inhibit these pathways and delay the expansion of AAA. We discuss newly patented agents that may have a beneficial role in preventing the progression of AAA.