{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T05:54:41Z","timestamp":1773035681720,"version":"3.50.1"},"reference-count":42,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2014,12,17]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Increasing evidence indicates that proteotoxicity plays a pathophysiologic role in experimental and human cardiomyopathy. In organ\u2010specific amyloidoses, soluble protein oligomers are the primary cytotoxic species in the process of protein aggregation. While isolated atrial amyloidosis can develop with aging, the presence of preamyloid oligomers (\n              <jats:styled-content style=\"fixed-case\">PAO<\/jats:styled-content>\n              s) in atrial tissue has not been previously investigated.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              Atrial samples were collected during elective cardiac surgery in patients without a history of atrial arrhythmias, congestive heart failure, cardiomyopathy, or amyloidosis. Immunohistochemistry was performed for\n              <jats:styled-content style=\"fixed-case\">PAO<\/jats:styled-content>\n              s using a conformation\u2010specific antibody, as well as for candidate proteins identified previously in isolated atrial amyloidosis. Using a myocardium\u2010specific marker, the fraction of myocardium colocalizing with\n              <jats:styled-content style=\"fixed-case\">PAO<\/jats:styled-content>\n              s (\n              <jats:styled-content style=\"fixed-case\">PAO<\/jats:styled-content>\n              burden) was quantified (green\/red ratio). Atrial samples were obtained from 92 patients, with a mean age of 61.7\u00b113.8\u00a0years. Most patients (62%) were male, 23% had diabetes, 72% had hypertension, and 42% had coronary artery disease. A majority (n=62) underwent aortic valve replacement, with fewer undergoing coronary artery bypass grafting (n=34) or mitral valve replacement\/repair (n=24). Immunostaining detected intracellular\n              <jats:styled-content style=\"fixed-case\">PAO<\/jats:styled-content>\n              s in a majority of atrial samples, with a heterogeneous distribution throughout the myocardium. Mean green\/red ratio value for the samples was 0.11\u00b10.1 (range 0.03 to 0.77), with a value \u22650.05 in 74 patients. Atrial natriuretic peptide colocalized with\n              <jats:styled-content style=\"fixed-case\">PAO<\/jats:styled-content>\n              s in myocardium, whereas transthyretin was located in the interstitium. Adjusting for multiple covariates,\n              <jats:styled-content style=\"fixed-case\">PAO<\/jats:styled-content>\n              burden was independently associated with the presence of hypertension.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p xml:lang=\"en\">PAOs are frequently detected in human atrium, where their presence is associated with clinical hypertension.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.114.001384","type":"journal-article","created":{"date-parts":[[2014,12,3]],"date-time":"2014-12-03T06:12:20Z","timestamp":1417587140000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":13,"title":["Hypertension Is Associated With Preamyloid Oligomers in Human Atrium: A Missing Link in Atrial Pathophysiology?"],"prefix":"10.1161","volume":"3","author":[{"given":"Tatiana N.","family":"Sidorova","sequence":"first","affiliation":[{"name":"Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa C.","family":"Mace","sequence":"additional","affiliation":[{"name":"Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"K. Sam","family":"Wells","sequence":"additional","affiliation":[{"name":"Departments of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Liudmila V.","family":"Yermalitskaya","sequence":"additional","affiliation":[{"name":"Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pei\u2010Fang","family":"Su","sequence":"additional","affiliation":[{"name":"Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yu","family":"Shyr","sequence":"additional","affiliation":[{"name":"Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James B.","family":"Atkinson","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Agnes B.","family":"Fogo","sequence":"additional","affiliation":[{"name":"Departments of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joseph K.","family":"Prinsen","sequence":"additional","affiliation":[{"name":"Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John G.","family":"Byrne","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael R.","family":"Petracek","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"James P.","family":"Greelish","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven J.","family":"Hoff","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen K.","family":"Ball","sequence":"additional","affiliation":[{"name":"Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Charles G.","family":"Glabe","sequence":"additional","affiliation":[{"name":"University of California, Irvine CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nancy J.","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joey V.","family":"Barnett","sequence":"additional","affiliation":[{"name":"Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Katherine T.","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2014.02.555"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijcard.2012.12.093"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2010.09.049"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cjca.2013.07.679"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-2236(00)01749-5"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000192103.24796.42"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra1106180"},{"key":"e_1_3_4_9_2","first-page":"1697","volume-title":"Kelley's Textbook of Rheumatology","author":"Seldin DC","year":"2005","unstructured":"Seldin DC, Skinner M. 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