{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:06:39Z","timestamp":1785420399025,"version":"3.56.0"},"reference-count":41,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T00:00:00Z","timestamp":1778544000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL164941"],"award-info":[{"award-number":["R01HL164941"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL122865"],"award-info":[{"award-number":["R01HL122865"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R01HL164941"],"award-info":[{"award-number":["R01HL164941"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01HL122865"],"award-info":[{"award-number":["R01HL122865"]}],"id":[{"id":"https:\/\/ror.org\/012pb6c26","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000049","name":"National Institute on Aging","doi-asserted-by":"publisher","award":["R03AG070784"],"award-info":[{"award-number":["R03AG070784"]}],"id":[{"id":"10.13039\/100000049","id-type":"DOI","asserted-by":"publisher"}]},{"award":["R03AG070784"],"award-info":[{"award-number":["R03AG070784"]}],"id":[{"id":"https:\/\/ror.org\/049v75w11","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Type-1 ryanodine receptor (RyR1) is essential for skeletal muscle contraction. This Ca2+ release channel is expressed in cardiac myocytes; however, its function remains elusive. Cardiac-specific RyR1 overexpression (OE) mice were generated under the cardiac-specific Myh6 promoter. Cardiac hypertrophy (CH), cardiac functions, and mechanistic changes in RyR1 OE and control (wildtype, WT) mice were assessed using hematoxylin and eosin staining, echocardiography, electrocardiogram, quantitative RT-PCR, Western blotting, [3H]-ryanodine binding assay, confocal microscope, ROS dye Amplex Red and 2\u2032,7\u2032-dichlorofluorescein diacetate. RyR1 OE mice had increased whole heart, left ventricular weight, and left ventricular wall thickness, but decreased cardiac output and stroke volume, thereby presenting CH and heart failure (HF). CH markers like ANF, BNF, and aSKA mRNAs were increased in RyR1 OE heart. RyR1, but not RyR2 or RyR3, expression was increased in the RyR1 OE mouse heart. Similar results were found in mice with TAC-induced CH. RyR1, but not RyR2 mRNA, was increased in cardiac muscle from dogs and humans with CH and\/or HF. Maximum [3H]-ryanodine binding was increased, whereas the binding dissociation constant decreased in left ventricular cardiomyocytes from RyR1 OE mice. RyR2-dependent Ca2+ sparks were increased, which was blocked by riluzole, a small molecule known to inhibit RyR2. Consistently, ROS was remarkably increased in RyR1 OE cardiac cells. We first generated cardiac-specific RyR1 OE mice; these mice had CH, HF, and increased RyR1 expression with no RyR2 or RyR3 alteration. Similar changes were observed in mice, dogs, and humans with CH and HF. Increased mitochondrial ROS-dependent RyR2 Ca2+ release was essential for RyR1-induced CH and HF.<\/jats:p>","DOI":"10.3390\/ijms27104291","type":"journal-article","created":{"date-parts":[[2026,5,12]],"date-time":"2026-05-12T16:04:36Z","timestamp":1778601876000},"page":"4291","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Type-1 Ryanodine Receptor Plays an Important Role in Cardiac Hypertrophy and Heart Failure by Increasing Type-2 Ryanodine Receptor-Mediated Calcium Release"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2674-7116","authenticated-orcid":false,"given":"Yong-Xiao","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7736-9645","authenticated-orcid":false,"given":"Ed Wilson","family":"Santos","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarahann","family":"Mistretta","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harold A.","family":"Singer","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3838-3601","authenticated-orcid":false,"given":"Shey-Shing","family":"Sheu","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Department of Medicine, Sidney Kimmel Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Min","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Molecular and Cellular Physiology, Albany Medical College, Albany, NY 12208, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,12]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Wang, Y.X. 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