{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T00:21:32Z","timestamp":1789172492799,"version":"build-2803163510"},"reference-count":43,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2017,5]]},"abstract":"\n Background<\/jats:title>\n \n Heart failure is a common secondary complication following a myocardial infarction (\n MI<\/jats:styled-content>\n ), characterized by impaired cardiac contraction and t\u2010tubule (t\u2010t) loss. However, post\u2010\n MI<\/jats:styled-content>\n nano\u2010scale morphological changes to the remaining t\u2010ts are poorly understood.\n <\/jats:p>\n <\/jats:sec>\n \n Method and Results<\/jats:title>\n \n We utilized a porcine model of\n MI<\/jats:styled-content>\n , using a nonlethal microembolization method to generate controlled microinfarcts. Using serial block face scanning electron microscopy, we report that post\u2010\n MI<\/jats:styled-content>\n , after mild left\u2010ventricular dysfunction has developed, t\u2010ts are not only lost in the peri\u2010infarct region, but also the remnant t\u2010ts form enlarged, highly branched disordered structures, containing a dense intricate inner membrane. Biochemical and proteomics analyses showed that the calcium release channel, ryanodine receptor 2 (RyR2), abundance is unchanged, but junctophilin\u20102 (\n JP<\/jats:styled-content>\n 2), important for maintaining t\u2010t trajectory, is depressed (\u22120.5\u00d7) in keeping with the t\u2010ts being disorganized. However, immunolabeling shows that populations of RyR2 and\n JP<\/jats:styled-content>\n 2 remain associated with the remodeled t\u2010ts. The bridging integrator 1 protein (\n BIN<\/jats:styled-content>\n \u20101), a regulator of tubulogensis, is upregulated (+5.4\u00d7), consistent with an overdeveloped internal membrane system, a feature not present in control t\u2010ts. Importantly, we have determined that t\u2010ts, in the remote region, are narrowed and also contain dense membrane folds (\n BIN<\/jats:styled-content>\n \u20101 is up\u2010regulated +3.4\u00d7), whereas the t\u2010ts have a radial organization comparable to control\n JP<\/jats:styled-content>\n 2 is upregulated +1.7\u00d7.\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n This study reveals previously unidentified remodeling of the t\u2010t nano\u2010architecture in the post\u2010\n MI<\/jats:styled-content>\n heart that extends to the remote region. Our findings highlight that targeting\n JP<\/jats:styled-content>\n 2 may be beneficial for preserving the orientation of the t\u2010ts, attenuating the development of hypocontractility post\u2010\n MI<\/jats:styled-content>\n .\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.116.004834","type":"journal-article","created":{"date-parts":[[2017,5,4]],"date-time":"2017-05-04T20:25:39Z","timestamp":1493929539000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":43,"title":["Post\u2010Myocardial Infarction T\u2010tubules Form Enlarged Branched Structures With Dysregulation of Junctophilin\u20102 and Bridging Integrator 1 (BIN\u20101)"],"prefix":"10.1161","volume":"6","author":[{"given":"Christian","family":"Pinali","sequence":"first","affiliation":[{"name":"University of Manchester","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadim","family":"Malik","sequence":"additional","affiliation":[{"name":"University of Manchester","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. 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