Judge Daniel P, Dietz Harry C
Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Annu Rev Med. 2008;59:43-59. doi: 10.1146/annurev.med.59.103106.103801.
Marfan syndrome is a common inherited disorder of connective tissue caused by deficiency of the matrix protein fibrillin-1. Effective surgical therapy for the most life-threatening manifestation, aortic root aneurysm, has led to a nearly normal lifespan for affected individuals who are appropriately recognized and treated. Traditional medical therapies, such as beta-adrenergic receptor blockade, are used to slow pathologic aortic growth and decrease the risk of aortic dissection by decreasing hemodynamic stress. New insights regarding the pathogenesis of Marfan syndrome have developed from investigation of murine models of this disorder. Fibrillin-1 deficiency is associated with excess signaling by transforming growth factor beta (TGFbeta). TGFbeta antagonists have shown great success in improving or preventing several manifestations of Marfan syndrome in these mice, including aortic aneurysm. These results highlight the potential for development of targeted therapies based on discovery of disease genes and interrogation of pathogenesis in murine models.
马凡综合征是一种常见的遗传性结缔组织疾病，由基质蛋白原纤蛋白-1缺乏引起。针对最危及生命的表现——主动脉根部瘤的有效手术治疗，已使得到恰当诊断和治疗的患者拥有接近正常的寿命。传统医学疗法，如β-肾上腺素能受体阻滞剂，被用于减缓病理性主动脉生长，并通过降低血流动力学应激来降低主动脉夹层的风险。对该疾病小鼠模型的研究产生了关于马凡综合征发病机制的新见解。原纤蛋白-1缺乏与转化生长因子β（TGFβ）的过度信号传导有关。TGFβ拮抗剂已在改善或预防这些小鼠马凡综合征的几种表现（包括主动脉瘤）方面取得了巨大成功。这些结果凸显了基于疾病基因发现和小鼠模型发病机制研究开发靶向治疗方法的潜力。
