{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T06:24:19Z","timestamp":1790922259057,"version":"4.1.0"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"21","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[2008,5,27]]},"abstract":"<jats:p>\n                    <jats:bold>\n                      <jats:italic>Background\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    To determine whether soluble preamyloid oligomers (PAOs) are toxic when expressed internally in the cardiomyocyte, we tested the hypothesis that cardiomyocyte-restricted expression and accumulation of a known PAO is cytotoxic and sufficient to cause heart failure.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Methods and Results\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    Intracellular PAOs, the entities believed to cause toxicity in many neurodegenerative diseases, have been observed in cardiomyocytes derived from mouse and human heart failure samples. Long (&gt;50) polyglutamine (PQ) repeats form PAOs and cause neurotoxicity in Huntington disease and other neurodegenerative diseases, whereas shorter PQ peptides are benign. We created transgenic mice in which cardiomyocyte-autonomous expression of an 83 residue\u2013long PQ repeat (PQ83) or a non\u2013amyloid-forming peptide of 19 PQ repeats (PQ19) as a nonpathological control was expressed. A PQ83 line with relatively low levels of expression was generated, along with a PQ19 line that expressed \u22489-fold the levels observed in the PQ83 line. Hearts expressing PQ83 exhibited reduced cardiac function and dilation by 5 months, and all mice died by 8 months, whereas PQ19 mice had normal cardiac function, morphology, and life span. PQ83 protein accumulated within aggresomes with PAO-specific staining. The PQ83 hearts showed increased autophagosomal and lysosomal content but also showed markers of necrotic death, including inflammatory cell infiltration and increased sarcolemmal permeability.\n                  <\/jats:p>\n                  <jats:p>\n                    <jats:bold>\n                      <jats:italic>Conclusions\u2014<\/jats:italic>\n                    <\/jats:bold>\n                    The data confirm the hypothesis that expression of an exogenous PAO-forming peptide is toxic to cardiomyocytes and is sufficient to cause cardiomyocyte loss and heart failure in a murine model.\n                  <\/jats:p>","DOI":"10.1161\/circulationaha.107.750232","type":"journal-article","created":{"date-parts":[[2008,5,19]],"date-time":"2008-05-19T20:53:31Z","timestamp":1211230411000},"page":"2743-2751","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":120,"title":["Cardiomyocyte Expression of a Polyglutamine Preamyloid Oligomer Causes Heart Failure"],"prefix":"10.1161","volume":"117","author":[{"given":"J. Scott","family":"Pattison","sequence":"first","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Atsushi","family":"Sanbe","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alina","family":"Maloyan","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanna","family":"Osinska","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raisa","family":"Klevitsky","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, Ohio."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey","family":"Robbins","sequence":"additional","affiliation":[{"name":"From the Department of Pediatrics, Division of Molecular Cardiovascular Biology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, 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