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Hypertension is associated with preamyloid oligomers in human atrium: a missing link in atrial pathophysiology?
Sidorova, Tatiana N; Mace, Lisa C; Wells, K Sam; Yermalitskaya, Liudmila V; Su, Pei-Fang; Shyr, Yu; Atkinson, James B; Fogo, Agnes B; Prinsen, Joseph K; Byrne, John G; Petracek, Michael R; Greelish, James P; Hoff, Steven J; Ball, Stephen K; Glabe, Charles G; Brown, Nancy J; Barnett, Joey V; Murray, Katherine T.
Afiliación
  • Sidorova TN; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (T.N.S., L.C.M., L.V.Y., J.K.P., N.J.B., J.V.B., K.T.M.).
  • Mace LC; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (T.N.S., L.C.M., L.V.Y., J.K.P., N.J.B., J.V.B., K.T.M.).
  • Wells KS; Departments of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN (S.W.).
  • Yermalitskaya LV; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (T.N.S., L.C.M., L.V.Y., J.K.P., N.J.B., J.V.B., K.T.M.).
  • Su PF; Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN (P.F.S., Y.S.).
  • Shyr Y; Center for Quantitative Sciences, Vanderbilt University School of Medicine, Nashville, TN (P.F.S., Y.S.).
  • Atkinson JB; Departments of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN (J.B.A., A.B.F.).
  • Fogo AB; Departments of Pathology, Microbiology, and Immunology, Vanderbilt University School of Medicine, Nashville, TN (J.B.A., A.B.F.).
  • Prinsen JK; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (T.N.S., L.C.M., L.V.Y., J.K.P., N.J.B., J.V.B., K.T.M.).
  • Byrne JG; Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, TN (J.G.B., M.R.P., J.P.G., S.J.H., S.K.B.).
  • Petracek MR; Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, TN (J.G.B., M.R.P., J.P.G., S.J.H., S.K.B.).
  • Greelish JP; Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, TN (J.G.B., M.R.P., J.P.G., S.J.H., S.K.B.).
  • Hoff SJ; Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, TN (J.G.B., M.R.P., J.P.G., S.J.H., S.K.B.).
  • Ball SK; Department of Cardiac Surgery, Vanderbilt University School of Medicine, Nashville, TN (J.G.B., M.R.P., J.P.G., S.J.H., S.K.B.).
  • Glabe CG; University of California, IrvineCA (C.G.G.).
  • Brown NJ; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (T.N.S., L.C.M., L.V.Y., J.K.P., N.J.B., J.V.B., K.T.M.).
  • Barnett JV; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (T.N.S., L.C.M., L.V.Y., J.K.P., N.J.B., J.V.B., K.T.M.).
  • Murray KT; Department of Medicine and Pharmacology, Vanderbilt University School of Medicine, Nashville, TN (T.N.S., L.C.M., L.V.Y., J.K.P., N.J.B., J.V.B., K.T.M.).
J Am Heart Assoc ; 3(6): e001384, 2014 Dec 02.
Article en En | MEDLINE | ID: mdl-25468655
BACKGROUND: Increasing evidence indicates that proteotoxicity plays a pathophysiologic role in experimental and human cardiomyopathy. In organ-specific 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 (PAOs) in atrial tissue has not been previously investigated. METHODS AND RESULTS: 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 PAOs using a conformation-specific antibody, as well as for candidate proteins identified previously in isolated atrial amyloidosis. Using a myocardium-specific marker, the fraction of myocardium colocalizing with PAOs (PAO burden) was quantified (green/red ratio). Atrial samples were obtained from 92 patients, with a mean age of 61.7±13.8 years. 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 PAOs in a majority of atrial samples, with a heterogeneous distribution throughout the myocardium. Mean green/red ratio value for the samples was 0.11±0.1 (range 0.03 to 0.77), with a value ≥0.05 in 74 patients. Atrial natriuretic peptide colocalized with PAOs in myocardium, whereas transthyretin was located in the interstitium. Adjusting for multiple covariates, PAO burden was independently associated with the presence of hypertension. CONCLUSION: PAOs are frequently detected in human atrium, where their presence is associated with clinical hypertension.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Función Atrial / Precursor de Proteína beta-Amiloide / Atrios Cardíacos / Hipertensión Tipo de estudio: Clinical_trials / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Am Heart Assoc Año: 2014 Tipo del documento: Article

Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Función Atrial / Precursor de Proteína beta-Amiloide / Atrios Cardíacos / Hipertensión Tipo de estudio: Clinical_trials / Prognostic_studies / Risk_factors_studies Límite: Aged / Female / Humans / Male / Middle aged Idioma: En Revista: J Am Heart Assoc Año: 2014 Tipo del documento: Article