Related Experiment Video
Updated: Jan 9, 2026
Estimating Bilateral Atrial Function by Cardiovascular Magnetic Resonance Feature Tracking in Patients with Paroxysmal Atrial Fibrillation
Published on: July 20, 2022
Hypertension is associated with preamyloid oligomers in human atrium: a missing link in atrial pathophysiology?
Tatiana N Sidorova1, Lisa C Mace1, K Sam Wells2
1Department 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.).
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.
Insights
Pre-amyloid oligomers (PAOs) are common in human atrial tissue and linked to hypertension. This study investigated PAOs in atria, finding their presence correlates with this common cardiovascular risk factor.
Area of Science:
- Cardiology
- Proteotoxicity
- Amyloidosis
Background:
- Proteotoxicity contributes to cardiomyopathy.
- Soluble protein oligomers are cytotoxic species in protein aggregation.
- Pre-amyloid oligomers (PAOs) in atrial tissue have not been previously investigated.
Purpose of the Study:
- To investigate the presence and distribution of PAOs in human atrial tissue.
- To determine the association between PAO burden and clinical factors, including hypertension.
Main Methods:
- Collected atrial samples from 92 patients undergoing cardiac surgery.
- Used immunohistochemistry to detect PAOs and candidate proteins.
- Quantified PAO burden using a myocardium-specific marker and green/red ratio.
Main Results:
- Intracellular PAOs were detected in a majority of atrial samples.
- PAO burden was heterogeneous throughout the myocardium.
- PAO burden was independently associated with hypertension.
Conclusions:
- PAOs are frequently detected in human atrium.
- The presence of PAOs in the atrium is associated with clinical hypertension.
More Related Videos
08:31Isolation of Atrial Cardiomyocytes from a Rat Model of Metabolic Syndrome-related Heart Failure with Preserved Ejection Fraction
Published on: July 26, 2018
10:53Isolation of Human Atrial Myocytes for Simultaneous Measurements of Ca2+ Transients and Membrane Currents
Published on: July 3, 2013