title: Glycosaminoglycan metabolism defects and atherosclerosis: frequent association of endothelial dysfunction in patients with Mucopolysaccharidosis.
abstract: 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.
authors.affiliation: 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, syano@usc.edu.
authors.forename: Shoji
authors.initials: S
authors.lastname: Yano
authors.forename: Kathryn
authors.initials: K
authors.lastname: Moseley
authors.forename: Lawrence
authors.initials: L
authors.lastname: Wong
authors.forename: Claudia
authors.initials: C
authors.lastname: Castelnovi
authors.forename: Colleen
authors.initials: C
authors.lastname: Azen
authors.forename: Zdena
authors.initials: Z
authors.lastname: Pavlova
mesh_terms: D000293:Adolescent; D000328:Adult; D050197:Atherosclerosis / Q000378:metabolism* / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006025:Glycosaminoglycans / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009083:Mucopolysaccharidoses / Q000378:metabolism* / Q000473:pathology*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D055815:Young Adult
chemical_list: D006025:Glycosaminoglycans; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III
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