{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:54:24Z","timestamp":1787018064283,"version":"build-2736575974"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"19","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2009,5,19]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    In classic Fabry patients, accelerated coronary atherosclerosis and left ventricular hypertrophy manifest in the fourth decade; however, signs of cardiovascular disease also are observed later in life in \u201ccardiac variant\u201d patients and symptomatic female heterozygotes. These disturbances are caused by globotriaosylceramide (GL-3) accumulation in the heart resulting from lysosomal \u03b1-galactosidase A deficiency.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    We analyzed pretreatment and posttreatment endomyocardial biopsies from 58 Fabry patients enrolled in a 5-month, phase 3, double-blind, randomized, placebo-controlled trial, followed by a 54-month open-label extension study of recombinant human \u03b1-galactosidase A. Baseline evaluations revealed GL-3 deposits in interstitial capillary endothelial cells and large, laminated inclusions within cardiomyocytes. In this study, we evaluated microvascular GL-3 clearance; no clearance of GL-3 was observed in the cardiomyocytes during this trial. Five months of recombinant human \u03b1-galactosidase A treatment in the phase 3 trial resulted in complete microvascular clearance of GL-3 from 72% of treated patients compared with only 3% of placebo patients (\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.001). The placebo group achieved similar results after 6 months of treatment in the open-label trial. In addition, the capillary endothelium remained free of GL-3 for up to 60 months in 6 of 8 patients who consented to an end-of-study biopsy.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    The findings suggest that long-term treatment with recombinant human \u03b1-galactosidase A may halt the progression of vascular pathology and prevent the clinical manifestations of atherosclerotic disease. This histopathological study should be a useful guide for clinicians and pathologists who diagnose and follow Fabry patients.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.108.841494","type":"journal-article","created":{"date-parts":[[2009,5,4]],"date-time":"2009-05-04T21:53:48Z","timestamp":1241474028000},"page":"2561-2567","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":134,"title":["Cardiac Microvascular Pathology in Fabry Disease"],"prefix":"10.1161","volume":"119","author":[{"given":"Beth L.","family":"Thurberg","sequence":"first","affiliation":[{"name":"From the Departments of Pathology and Preclinical Biology, Genzyme Corporation, Cambridge, Mass (B.L.T., M.W.O.); Department of Pathology, Mount Sinai School of Medicine, New York, NY (J.T.F., R.E.G.); Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Mass (R.M.); and Department of Pathology, Massachusetts General Hospital, Boston, Mass (T.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John T.","family":"Fallon","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Preclinical Biology, Genzyme Corporation, Cambridge, Mass (B.L.T., M.W.O.); Department of Pathology, Mount Sinai School of Medicine, New York, NY (J.T.F., R.E.G.); Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Mass (R.M.); and Department of Pathology, Massachusetts General Hospital, Boston, Mass (T.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Mitchell","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Preclinical Biology, Genzyme Corporation, Cambridge, Mass (B.L.T., M.W.O.); Department of Pathology, Mount Sinai School of Medicine, New York, NY (J.T.F., R.E.G.); Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Mass (R.M.); and Department of Pathology, Massachusetts General Hospital, Boston, Mass (T.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Aretz","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Preclinical Biology, Genzyme Corporation, Cambridge, Mass (B.L.T., M.W.O.); Department of Pathology, Mount Sinai School of Medicine, New York, NY (J.T.F., R.E.G.); Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Mass (R.M.); and Department of Pathology, Massachusetts General Hospital, Boston, Mass (T.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald E.","family":"Gordon","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Preclinical Biology, Genzyme Corporation, Cambridge, Mass (B.L.T., M.W.O.); Department of Pathology, Mount Sinai School of Medicine, New York, NY (J.T.F., R.E.G.); Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Mass (R.M.); and Department of Pathology, Massachusetts General Hospital, Boston, Mass (T.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael W.","family":"O'Callaghan","sequence":"additional","affiliation":[{"name":"From the Departments of Pathology and Preclinical Biology, Genzyme Corporation, Cambridge, Mass (B.L.T., M.W.O.); Department of Pathology, Mount Sinai School of Medicine, New York, NY (J.T.F., R.E.G.); Department of Pathology, Brigham and Women\u2019s Hospital and Harvard Medical School, Boston, Mass (R.M.); and Department of Pathology, Massachusetts General Hospital, Boston, Mass (T.A.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2002.00675.x"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.0022-202X.2004.22425.x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2007.02.006"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.2169\/internalmedicine.36.327"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1399-0004.1987.tb02820.x"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200002)47:2<229::AID-ANA13>3.0.CO;2-T"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/s11745-005-1488-8"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.107.149179"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000012626.81324.38"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2007.06.062"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/GIM.0b013e31802d8321"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-007-0521-2"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2007.09.013"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.2004.054015"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.7326\/0003-4819-117-3-221"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00428-005-0089-x"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1042\/bj1040340"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9150(80)90081-7"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1139\/o81-057"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.bi.46.070177.004341"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2760(76)90152-1"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1023\/B:BOLI.0000045841.27968.06"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M413862200"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712309105"},{"key":"e_1_3_2_25_2","first-page":"63","volume":"451","year":"2006","unstructured":"Barbey F, Brakch N, Linhart A, Jeanrenaud X, Palecek T, Bultas J, Burnier M, Hayoz D. 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