Understanding abdominal aortic aneurysm.
Understanding abdominal aortic aneurysm.
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DOI：
10.1056/nejmcibr0905244
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发表时间：
2009-09-10
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影响因子：
--
通讯作者：
Weintraub NL
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作者：
Weintraub NL
腹主动脉瘤发生在高达9%的65岁以上的成年人中，这些动脉瘤的破裂在美国每年造成约15，000人死亡。1每年约有33，000名患者接受腹主动脉瘤修复术，并伴有相关疾病、死亡和医疗保健费用。吸烟是一个主要的危险因素。尽管腹主动脉瘤患者建议积极治疗高血压和高脂血症，但这些疾病的治疗对动脉瘤生长和破裂几乎没有影响。在这种情况下，Satoh及其同事最近的一项研究2受到欢迎，因为它为腹主动脉瘤的形成提供了新的线索，从而重新点燃了人们对十多年前被证明可以防止实验性动脉瘤形成的治疗的兴趣。流行病学和病理学研究对腹主动脉瘤的病因几乎没有线索。虽然腹主动脉瘤经常发生在动脉粥样硬化患者中，并且这两种疾病过程具有几个共同的风险因素，但动脉粥样硬化病变主要位于内膜，而动脉瘤主要涉及中膜和外膜。动脉粥样硬化的标志性病理特征是泡沫细胞形成，而动脉瘤的典型特征是强烈的氧化应激、炎症、基质降解和平滑肌细胞凋亡。3基质金属蛋白酶抑制剂目前正在人类动脉瘤疾病中进行测试，但其疗效可能有限，部分原因是它们仅针对疾病过程的一个方面;因此，靶向有助于动脉瘤病理过程多个方面的因素可能会有更大的益处。动物模型研究表明，血管紧张素II诱导血管氧化应激、炎症、基质降解和平滑肌细胞凋亡，并在实验上促进动脉瘤形成。4对人体的研究也表明血管紧张素II在疾病的发病机制中起作用。然而，将这些病理过程联系在一起以产生腹主动脉瘤的细胞机制仍有待阐明。
Abdominal aortic aneurysms occur in up to 9% of adults older than 65 years of age, and the rupture of these aneurysms accounts for about 15,000 deaths in the United States annually. 1 Approximately 33,000 patients undergo repair of abdominal aortic aneurysms each year, with associated illness, death, and health care costs. Smoking is a major risk factor. Although aggressive management of hypertension and hyperlipidemia is recommended in patients with abdominal aortic aneurysms, therapies for these conditions have little effect on aneurysm growth and rupture. In this context, a recent study by Satoh and colleagues2 is welcome because it sheds new light on how abdominal aortic aneurysms form and thereby rekindles interest in a therapy that was shown to protect against experimental aneurysm formation more than a decade ago.Epidemiologic and pathological studies have yielded few clues to the cause of abdominal aortic aneurysms. Although abdominal aortic aneurysms frequently occur in patients with atherosclerosis and the two disease processes share several common risk factors, atherosclerotic lesions are predominantly intimal in location, whereas the media and adventitia are primarily involved in aneurysms. The hallmark pathologic feature of atherosclerosis is foam-cell formation, whereas aneurysms are typified by intense oxidative stress, inflammation, matrix degradation, and apoptosis of smooth-muscle cells. 3 Inhibitors of matrix metalloproteinase are currently being tested in human aneurysmal disease, but their efficacy may be limited, in part because they are directed toward only one aspect of the disease process; thus, targeting factors that contribute to multiple aspects of the pathologic process of aneurysms would probably be of greater benefit. Studies in animal models have shown that angiotensin II induces vascular oxidative stress, inflammation, matrix degradation, and apoptosis of smooth-muscle cells and contributes experimentally to aneurysm formation. 4 Studies in humans also suggest a role for angiotensin II in the pathogenesis of the disease. However, the cellular mechanisms that link these pathologic processes together to produce abdominal aortic aneurysms remain to be elucidated.