{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T21:37:36Z","timestamp":1770068256790,"version":"3.49.0"},"reference-count":63,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation"],"published-print":{"date-parts":[[1998,1,20]]},"abstract":"<jats:p>\n            <jats:italic>Background<\/jats:italic>\n            \u2014Rapid ventricular pacing in dogs is characterized by a dilated myopathy in which myocyte cell death by apoptosis may play a significant role in the impairment of cardiac pump function. However, the molecular mechanisms implicated in the modulation of programmed cell death under this setting remain to be identified. Moreover, questions have been raised on the specificity and sensitivity of the histochemical detection of DNA strand breaks in nuclei by the terminal deoxynucleotidyl transferase (TdT) reaction.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Methods and Results<\/jats:italic>\n            \u2014Changes in the expression of\n            <jats:italic>Bcl<\/jats:italic>\n            -2 and\n            <jats:italic>Bax<\/jats:italic>\n            and their transcriptional regulator, p53, were determined by Western blot analysis in myocytes isolated from dogs affected by pacing-induced heart failure. A mobility shift assay for p53 binding activity was also performed. In addition, apoptosis was measured by confocal microscopy, which allowed the simultaneous detection of chromatin alterations and DNA damage. p53 DNA binding activity to the\n            <jats:italic>bax<\/jats:italic>\n            promoter was increased in nuclear extracts from myocytes obtained from failing hearts, and this response was associated with enhanced expression of\n            <jats:italic>Bax<\/jats:italic>\n            protein, 52%, and attenuation of\n            <jats:italic>Bcl<\/jats:italic>\n            -2, \u221292%. Immunolabeling of p53 in myocyte nuclei, measured by confocal microscopy, was 100% higher in cells from paced hearts. The combination of the TdT assay and confocal microscopy demonstrated that 20 myocyte nuclei per 10\n            <jats:sup>6<\/jats:sup>\n            were undergoing apoptosis in control myocardium and 4000 per 10\n            <jats:sup>6<\/jats:sup>\n            after pacing. Moreover, DNA laddering was shown in myocytes by agarose gel electrophoresis of DNA fragments.\n          <\/jats:p>\n          <jats:p>\n            <jats:italic>Conclusions<\/jats:italic>\n            \u2014The activation of p53 and p53-dependent genes may be critical in the modulation of myocyte apoptosis in pacing-induced heart failure.\n          <\/jats:p>","DOI":"10.1161\/01.cir.97.2.194","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:41:02Z","timestamp":1339461662000},"page":"194-203","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":87,"title":["Pacing-Induced Heart Failure in Dogs Enhances the Expression of p53 and p53-Dependent Genes in Ventricular Myocytes"],"prefix":"10.1161","volume":"97","author":[{"given":"Annarosa","family":"Leri","sequence":"first","affiliation":[{"name":"From the Departments of Medicine and Physiology, New York Medical College, Valhalla, NY; the Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY; and the Departments of Pathology, Anatomy, and Cell Biology and Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Philadelphia, Pa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Physiology, New York Medical College, Valhalla, NY; the Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY; and the Departments of Pathology, Anatomy, and Cell Biology and Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Philadelphia, Pa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ashwani","family":"Malhotra","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Physiology, New York Medical College, Valhalla, NY; the Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY; and the Departments of Pathology, Anatomy, and Cell Biology and Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Philadelphia, Pa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiong","family":"Li","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Physiology, New York Medical College, Valhalla, NY; the Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY; and the Departments of Pathology, Anatomy, and Cell Biology and Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Philadelphia, Pa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Stiegler","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Physiology, New York Medical College, Valhalla, NY; the Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY; and the Departments of Pathology, Anatomy, and Cell Biology and Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Philadelphia, Pa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pier Paolo","family":"Claudio","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Physiology, New York Medical College, Valhalla, NY; the Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY; and the Departments of Pathology, Anatomy, and Cell Biology and Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Philadelphia, Pa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Giordano","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Physiology, New York Medical College, Valhalla, NY; the Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY; and the Departments of Pathology, Anatomy, and Cell Biology and Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Philadelphia, Pa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Kajstura","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Physiology, New York Medical College, Valhalla, NY; the Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY; and the Departments of Pathology, Anatomy, and Cell Biology and Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Philadelphia, Pa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas H.","family":"Hintze","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Physiology, New York Medical College, Valhalla, NY; the Department of Medicine, Montefiore Medical Center and Albert Einstein College of Medicine, New York, NY; and the Departments of Pathology, Anatomy, and Cell Biology and Institute for Cancer Research and Molecular Medicine, Jefferson Medical College, Philadelphia, Pa."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piero","family":"Anversa","sequence":"additional","affiliation":[{"name":"From the Departments of Medicine and Physiology, New York Medical College, Valhalla, NY; 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