Hypertension Is Associated With Preamyloid Oligomers in Human Atrium: A Missing Link in Atrial Pathophysiology?

Autor: Katherine T. Murray, Pei Fang Su, Tatiana N. Sidorova, Lisa C. Mace, Yu Shyr, Joey V. Barnett, James B. Atkinson, James P. Greelish, Agnes B. Fogo, K. Sam Wells, Charles G. Glabe, Stephen K. Ball, Liudmila V. Yermalitskaya, Joseph K. Prinsen, John G. Byrne, Nancy J. Brown, Steven J. Hoff, Michael R. Petracek
Rok vydání: 2014
Předmět:
Male
medicine.medical_specialty
medicine.medical_treatment
Cardiomyopathy
030204 cardiovascular system & hematology
preamyloid oligomers
Coronary artery disease
Amyloid beta-Protein Precursor
Protein Aggregates
03 medical and health sciences
0302 clinical medicine
Atrial natriuretic peptide
Internal medicine
atrial natriuretic peptide
medicine
Humans
Prealbumin
Arrhythmia and Electrophysiology
Isolated atrial amyloidosis
cardiovascular diseases
Heart Atria
Atrium (heart)
Aged
Randomized Controlled Trials as Topic
Original Research
030304 developmental biology
0303 health sciences
business.industry
Amyloidosis
Mitral valve replacement
amyloid
Middle Aged
Atrial Function
medicine.disease
Fibrosis
Immunohistochemistry
medicine.anatomical_structure
Heart failure
Hypertension
cardiovascular system
Cardiology
Female
Cardiology and Cardiovascular Medicine
business
Atrial Natriuretic Factor
atrium
Zdroj: Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease
ISSN: 2047-9980
Popis: 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 ( PAO s) 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 PAO s 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 PAO s ( 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 PAO 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±0.1 (range 0.03 to 0.77), with a value ≥0.05 in 74 patients. Atrial natriuretic peptide colocalized with PAO s 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.
Databáze: OpenAIRE
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