{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T03:49:24Z","timestamp":1772164164234,"version":"3.50.1"},"reference-count":37,"publisher":"American Physiological Society","issue":"4","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2009,4]]},"abstract":"\n The lysosomal storage disorder Fabry disease is characterized by excessive globotriaosylceramide (Gb3) accumulation in major organs such as the heart and kidney. Defective lysosomal \u03b1-galactosidase A (Gla) is responsible for excessive Gb3 accumulation, and one cell sensitive to the effects of Gb3 accumulation is vascular endothelium. Endothelial dysfunction is associated with Fabry disease and excessive cellular Gb3. We previously demonstrated that excessive vascular Gb3 in a mouse model of Fabry disease, the Gla-knockout ( Gla\n \u2212\/0<\/jats:sup>\n ) mouse, results in abnormal vascular function, which includes abnormal endothelium-dependent contractions, a vascular phenomenon known to involve cyclooxygenase (COX). Therefore, we hypothesized that the vasculopathy in the Gla knockout mouse may be due to a vasoactive COX-derived product. To test this hypothesis, vascular reactivity experiments were performed in aortic rings from wild-type ( Gla\n +\/0<\/jats:sup>\n ) and Gla\n \u2212\/0<\/jats:sup>\n mice in the presence and absence of specific and nonspecific COX inhibitors. Specific inhibition of COX1 or COX2 in endothelium-intact rings from Gla\n \u2212\/0<\/jats:sup>\n mice decreased overall phenylephrine contractility compared with untreated Gla\n \u2212\/0<\/jats:sup>\n rings, whereas COX inhibitors had no effect on contractility in endothelium-denuded rings. Nonspecific inhibition of COX with indomethacin (10 \u03bcmol\/l) or COX1 inhibition with valeryl salicylate (3 mmol\/l) improved endothelial function in rings from Gla\n \u2212\/0<\/jats:sup>\n mice, but COX2 inhibition with NS-398 (1 \u03bcmol\/l) further increased endothelial dysfunction in rings from Gla\n \u2212\/0<\/jats:sup>\n mice. These results suggest that, in the Gla\n \u2212\/0<\/jats:sup>\n mice, COX1 and COX2 activity are increased and localized in the endothelium, producing vasopressor and vasorelaxant products, which contribute to the Fabry-related vasculopathy.\n <\/jats:p>","DOI":"10.1152\/ajpheart.00929.2008","type":"journal-article","created":{"date-parts":[[2009,2,7]],"date-time":"2009-02-07T04:03:03Z","timestamp":1233979383000},"page":"H1133-H1140","source":"Crossref","is-referenced-by-count":14,"title":["Differential involvement of COX1 and COX2 in the vasculopathy associated with the \u03b1-galactosidase A-knockout mouse"],"prefix":"10.1152","volume":"296","author":[{"given":"James L.","family":"Park","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liming","family":"Shu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James A.","family":"Shayman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"24","reference":[{"key":"R1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.32.7.1559"},{"key":"R2","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000163145.12707.63"},{"key":"R3","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.0000172688.26838.9f"},{"key":"R4","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.0000154550.15963.80"},{"key":"R5","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00628.2004"},{"key":"R6","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050493"},{"key":"R7","doi-asserted-by":"publisher","DOI":"10.1152\/ajplung.00215.2002"},{"key":"R8","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.300.2.393"},{"key":"R9","doi-asserted-by":"publisher","DOI":"10.1081\/CEH-100100073"},{"key":"R10","unstructured":"Desnick R\n , Ioannou Y, Eng C.\n \u03b1-Galactosidase A deficiency: Fabry disease. In:\n The Metabolic and Molecular Bases of Inherited Disease\n (8th ed.), edited by Scriver C, Beadet A, Sly W, and Valle D. New York: McGraw-Hill, 2001, p. 3733\u20133774."},{"key":"R11","doi-asserted-by":"publisher","DOI":"10.1097\/01.ASN.0000043901.45141.D4"},{"key":"R12","doi-asserted-by":"crossref","unstructured":"Elliott PM\n , Kindler H, Shah JS, Sachdev B, Rimoldi OE, Thaman R, Tome MT, McKenna WJ, Lee P, Camici PG.\n Coronary microvascular dysfunction in male patients with Anderson-Fabry disease and the effect of treatment with \u03b1-galactosidase A.\n Heart\n 92\n : 357\u2013360, 2006.","DOI":"10.1136\/hrt.2004.054015"},{"key":"R13","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00429.2004"},{"key":"R14","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2005.04.008"},{"key":"R15","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0473-y"},{"key":"R16","doi-asserted-by":"publisher","DOI":"10.1161\/hc3301.092790"},{"key":"R17","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0703632"},{"key":"R18","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00646.2007"},{"key":"R19","doi-asserted-by":"publisher","DOI":"10.1016\/S0014-2999(01)01140-2"},{"key":"R20","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-005-0563-2"},{"key":"R21","doi-asserted-by":"publisher","DOI":"10.1007\/s10545-006-0221-3"},{"key":"R22","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.8.4.344"},{"key":"R23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00289.2007"},{"key":"R24","doi-asserted-by":"publisher","DOI":"10.1161\/hc3801.096352"},{"key":"R25","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa050330"},{"key":"R26","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.94.6.2540"},{"key":"R27","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1681.2008.04984.x"},{"key":"R28","unstructured":"Shayman JA\n , Killen PD.\n Fabry disease. In:\n Molecular and Genetic Basis of Renal Disease\n , edited by Mount DB and Pollak MR. Philadelphia: Saunders Elsevier, 2008, p. 195\u2013199."},{"key":"R29","doi-asserted-by":"crossref","unstructured":"Shepherd JT\n , Katusic ZS.\n Endothelium-derived vasoactive factors. I. Endothelium-dependent relaxation.\n Hypertension\n 18\n Suppl\n III: 76\u201385, 1991.","DOI":"10.1161\/01.HYP.18.5_Suppl.III76"},{"key":"R30","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M111363200"},{"key":"R31","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.2005040383"},{"key":"R32","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M702436200"},{"key":"R33","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M303783200"},{"key":"R34","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01130.2005"},{"key":"R35","doi-asserted-by":"publisher","DOI":"10.1097\/01.fjc.0000187174.67661.67"},{"key":"R36","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjp.0706042"},{"key":"R37","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000129578.76799.75"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00929.2008","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T17:18:52Z","timestamp":1567963132000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00929.2008"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2009,4]]},"references-count":37,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2009,4]]}},"alternative-id":["10.1152\/ajpheart.00929.2008"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00929.2008","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1160339.620671","asserted-by":"object"}]},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,4]]}}}