Yano Shoji, Moseley Kathryn, Wong Lawrence, Castelnovi Claudia, Azen Colleen, Pavlova Zdena
Genetics Division, Department of Pediatrics, LAC+USC Medical Center, Keck School of Medicine, University of Southern California, 1801 Marengo Street General Laboratory Building, Room 1G-24, Los Angeles, CA, 90033, USA,
J Inherit Metab Dis. 2014 Mar;37(2):255-61. doi: 10.1007/s10545-013-9642-y. Epub 2013 Jul 27.
Cardiovascular lesions, including coronary artery stenosis, are frequently associated and can cause sudden death in patients with genetic defects of glycosaminoglycan (GAG) metabolism. Early diagnosis of coronary artery lesions is difficult, although potentially lifesaving. Histopathological similarities between atherosclerotic changes in adults and in patients with genetic GAG metabolism defects have been known. Atherosclerosis is the result of a complex process involving metabolism of GAGs and proteoglycans preceded by endothelial dysfunction as a key event. Decreased nitric oxide (NO) bioavailability is considered the hallmark of endothelial dysfunction. Reduced NO synthase (NOS) has been reported in atherosclerotic arteries. Impairment in reactive hyperemia-digital peripheral arterial tonometry (RH-PAT) with EndoPAT has been validated to correlate coronary microvascular function in patients with atherosclerosis. RH-PAT is thought to reflect endothelial NO production. Immunohistological staining of endothelial NOS was performed in the stenotic lesions in the coronary artery of a 3-year-old patient with Mucopolysaccharidosis-I, showing decreased activities. This prompted a study to measure endothelial function in patients with GAG metabolism defects for early diagnosis of endothelial dysfunction in the coronary arteries as an early sign of coronary artery changes. Evaluation by RH-PAT in 30 patients with variable genetic defects in GAG metabolism revealed significantly decreased Reactive Hyperemia Indexes compared with 12 controls. Evaluation of endothelial function with RH-PAT in patients with GAG metabolism defects may detect coronary artery lesions that can be underdiagnosed by the other measures such as coronary angiography. Use of this method may prove vital in the management of patients with GAG metabolism defects.
心血管病变，包括冠状动脉狭窄，常与糖胺聚糖（GAG）代谢遗传缺陷患者相关联，并可导致猝死。冠状动脉病变的早期诊断虽然可能挽救生命，但却很困难。已知成人动脉粥样硬化改变与遗传性GAG代谢缺陷患者的组织病理学相似性。动脉粥样硬化是一个复杂过程的结果，该过程涉及GAG和蛋白聚糖的代谢，内皮功能障碍是关键事件。一氧化氮（NO）生物利用度降低被认为是内皮功能障碍的标志。据报道，动脉粥样硬化动脉中一氧化氮合酶（NOS）减少。EndoPAT测量反应性充血-数字外周动脉张力测定法（RH-PAT）受损已被证实与动脉粥样硬化患者的冠状动脉微血管功能相关。RH-PAT被认为可反映内皮NO的产生。对一名3岁黏多糖贮积症I型患者冠状动脉狭窄病变进行内皮NOS免疫组织化学染色，结果显示活性降低。这促使开展一项研究，以测量GAG代谢缺陷患者的内皮功能，以便早期诊断冠状动脉内皮功能障碍，作为冠状动脉病变的早期迹象。对30名GAG代谢存在不同遗传缺陷的患者进行RH-PAT评估，结果显示与12名对照组相比，反应性充血指数显著降低。对GAG代谢缺陷患者使用RH-PAT评估内皮功能，可能检测出其他检查方法（如冠状动脉造影）可能漏诊的冠状动脉病变。使用这种方法可能对GAG代谢缺陷患者的管理至关重要。
