From the Division of Medical Genetics, Department of Internal Medicine, University of Texas Health Science Center at Houston, Houston, Texas, USA.
Genet Med. 2010 Apr;12(4):196-203. doi: 10.1097/GIM.0b013e3181cdd687.
Genetic predisposition to early onset of occlusive vascular diseases, including coronary artery disease, ischemic stroke, and Moyamoya disease, may represent varying presentations of a common underlying dysregulation of vascular smooth muscle cell proliferation. We discuss mutations in two genes, NF1 and ACTA2, which predispose affected individuals to diffuse and diverse vascular diseases. These patients show evidence of diffuse occlusive disease in multiple arterial beds or even develop seemingly diverse arterial pathologies, ranging from occlusions to arterial aneurysms. We also present the current evidence that both NF1 and ACTA2 mutations promote increased smooth muscle cell proliferation in vitro and in vivo, which leads us to propose that these diffuse and diverse vascular diseases are the outward signs of a more fundamental disease: a hyperplastic vasculomyopathy. We suggest that the concept of a hyperplastic vasculomyopathy offers a new approach not only to identifying mutated genes that lead to vascular diseases but also to counseling and possibly treating patients harboring such mutations. In other words, this framework may offer the opportunity to therapeutically target the inappropriate smooth muscle cell behavior that predisposes to a variety of vascular diseases throughout the arterial system.
遗传性易患早发性闭塞性血管疾病，包括冠状动脉疾病、缺血性中风和 moyamoya 病，可能代表血管平滑肌细胞增殖的常见潜在失调的不同表现。我们讨论了两个基因 NF1 和 ACTA2 的突变，这些突变使受影响的个体易患弥漫性和多样化的血管疾病。这些患者在多个动脉床中表现出弥漫性闭塞性疾病的证据，甚至发展出看似不同的动脉病理学，从闭塞到动脉动脉瘤。我们还提出了目前的证据，即 NF1 和 ACTA2 突变促进了体外和体内平滑肌细胞的过度增殖，这使我们提出这些弥漫性和多样化的血管疾病是一种更基本疾病的外在表现：增生性血管肌病。我们认为增生性血管肌病的概念不仅为识别导致血管疾病的突变基因提供了一种新方法，也为携带这些突变的患者提供了咨询和可能的治疗机会。换句话说，这个框架可能为治疗提供机会，针对导致整个动脉系统多种血管疾病的不适当平滑肌细胞行为。
