{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T15:58:40Z","timestamp":1779897520091,"version":"3.53.1"},"reference-count":34,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T00:00:00Z","timestamp":1646006400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002426","name":"Telethon Foundation","doi-asserted-by":"publisher","award":["Andrea Frustaci GGP17055"],"award-info":[{"award-number":["Andrea Frustaci GGP17055"]}],"id":[{"id":"10.13039\/501100002426","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["U54NS065768\/NS\/NINDS"],"award-info":[{"award-number":["U54NS065768\/NS\/NINDS"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The impact of enzyme replacement therapy (ERT) on cardiomyocytes and intestinal cells, affected by Fabry disease (FD), is still unclear. Methods: Six patients with FD, including five family members with GLA mutation c.666delC and one with GLA mutation c.658C &gt; T, manifesting cardiomyopathy and intestinal symptoms (abdominal pain, diarrhea and malabsorption) were included in the study. Clinical outcome, cardiac magnetic resonance (CMR), endomyocardial and gastro-intestinal biopsies were evaluated before and after 2 years of treatment with agalsidase-\u03b1 (0.2 mg\/kg every other week). Immunohistochemistry and Western blot assessments of mannose-6-phosphate receptors (IGF-II-R) on intestinal and myocardial frozen tissue were obtained at diagnosis and after 2 years of ERT. Results: After ERT left ventricular maximal wall thickness, ranging from pre (&lt;10.5 mm) to mild (&lt;15 mm) and moderate hypertrophy (16 mm), was not associated with significant changes at CMR. Degree of dyspnea, mean cardiomyocyte diameter and % vacuolated areas of cardiomyocytes, representing intracellular GL3, remained unmodified. In contrast, intestinal symptoms improved with disappearance of diarrhea, recovery of anemia and weight gain, correlating with near complete clearance of the enterocytes from GL3 inclusions. IGF-II-R expression was remarkably higher even at histochemistry in intestinal tissue compared with myocardium (p &lt; 0.001) either at baseline and after ERT, thus justifying intestinal recovery. Conclusions: Human cells affected by FD may respond differently to ERT: while cardiomyocytes retain their GL3 content after 2 years of treatment, gastro-intestinal cells show GL3 removal with recovery of function. This divergent response may be related to differences in cellular turnover, as well as tissue IGF-II-R expression.<\/jats:p>","DOI":"10.3390\/jcm11051344","type":"journal-article","created":{"date-parts":[[2022,2,28]],"date-time":"2022-02-28T20:11:14Z","timestamp":1646079074000},"page":"1344","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Divergent Impact of Enzyme Replacement Therapy on Human Cardiomyocytes and Enterocytes Affected by Fabry Disease: Correlation with Mannose-6-phosphate Receptor Expression"],"prefix":"10.3390","volume":"11","author":[{"given":"Andrea","family":"Frustaci","sequence":"first","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, La Sapienza University, 00100 Rome, Italy"},{"name":"Cellular and Molecular Cardiology Laboratory, IRCCS L. Spallanzani, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0904-6721","authenticated-orcid":false,"given":"Behzad","family":"Najafian","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Donato","sequence":"additional","affiliation":[{"name":"Department of Translational and Precision Medicine, La Sapienza University, 00100 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Verardo","sequence":"additional","affiliation":[{"name":"Cellular and Molecular Cardiology Laboratory, IRCCS L. Spallanzani, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristina","family":"Chimenti","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, La Sapienza University, 00100 Rome, Italy"},{"name":"Cellular and Molecular Cardiology Laboratory, IRCCS L. Spallanzani, 00149 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3150-6461","authenticated-orcid":false,"given":"Luigi","family":"Sansone","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Pathology, IRCCS San Raffaele Pisana, 88163 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9183-6206","authenticated-orcid":false,"given":"Manuel","family":"Belli","sequence":"additional","affiliation":[{"name":"Laboratory of Molecular and Cellular Pathology, IRCCS San Raffaele Pisana, 88163 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enza","family":"Vernucci","sequence":"additional","affiliation":[{"name":"Department of Clinical, Internal, Anesthesiologist and Cardiovascular Sciences, La Sapienza University, 00100 Rome, Italy"},{"name":"Laboratory of Molecular and Cellular Pathology, IRCCS San Raffaele Pisana, 88163 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5847-6015","authenticated-orcid":false,"given":"Matteo Antonio","family":"Russo","sequence":"additional","affiliation":[{"name":"MEBIC Consortium, San Raffaele Open University, 00166 Rome, Italy"},{"name":"IRCCS San Raffaele Pisana, 88163 Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,2,28]]},"reference":[{"key":"ref_1","unstructured":"Scriver, C.R., Al, B., Sly, W.S., and Valle, D. 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