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Heart Failure Reviews Nov 2023Cardiac amyloidosis (CA) occurs when the insoluble fibrils formed by misfolded precursor proteins deposit in cardiac tissues. The early clinical manifestations of CA are... (Review)
Review
Cardiac amyloidosis (CA) occurs when the insoluble fibrils formed by misfolded precursor proteins deposit in cardiac tissues. The early clinical manifestations of CA are not evident, but it is easy to progress to refractory heart failure with an inferior prognosis. Echocardiography is the most commonly adopted non-invasive modality of imaging to visualize cardiac structures and functions, and the preferred modality in the evaluation of patients with cardiac symptoms and suspected CA, which plays a vital role in the diagnosis, prognosis, and long-term management of CA. The present review summarizes the echocardiographic manifestations of CA, new echocardiographic techniques, and the application of multi-parametric echocardiographic models in CA diagnosis.
Topics: Humans; Cardiomyopathies; Echocardiography; Amyloidosis; Heart Diseases; Heart
PubMed: 37558934
DOI: 10.1007/s10741-023-10332-3 -
CMAJ : Canadian Medical Association... Dec 2022
Topics: Humans; Insulin; Amyloidosis; Hypoglycemic Agents
PubMed: 36507789
DOI: 10.1503/cmaj.220531 -
International Journal of Molecular... Dec 2022Amyloidoses are a group of diseases associated with deposits of amyloid fibrils in different tissues. So far, 36 different types of amyloidosis are known, each due to... (Review)
Review
Amyloidoses are a group of diseases associated with deposits of amyloid fibrils in different tissues. So far, 36 different types of amyloidosis are known, each due to the misfolding and accumulation of a specific protein. Amyloid deposits can be found in several organs, including the heart, brain, kidneys, and spleen, and can affect single or multiple organs. Generally, amyloid-forming proteins become prone to aggregate due to genetic mutations, acquired environmental factors, excessive concentration, or post-translational modifications. Interestingly, amyloid aggregates are often composed of proteolytic fragments, derived from the degradation of precursor proteins by yet unidentified proteases, which display higher amyloidogenic tendency compared to precursor proteins, thus representing an important mechanism in the onset of amyloid-based diseases. In the present review, we summarize the current knowledge on the proteolytic susceptibility of three of the main human amyloidogenic proteins, i.e., transthyretin, β-amyloid precursor protein, and α-synuclein, in the onset of amyloidosis. We also highlight the role that proteolytic enzymes can play in the crosstalk between intestinal inflammation and amyloid-based diseases.
Topics: Humans; Proteolysis; Amyloidosis; Amyloid; Amyloid beta-Protein Precursor; Protein Precursors; Prealbumin; Peptide Hydrolases
PubMed: 36614141
DOI: 10.3390/ijms24010699 -
Journal of Nuclear Medicine : Official... Jul 2020Transthyretin and light-chain amyloidosis are the 2 main causes of cardiac amyloidosis. Recent developments in molecular imaging have transformed our ability to diagnose... (Review)
Review
Transthyretin and light-chain amyloidosis are the 2 main causes of cardiac amyloidosis. Recent developments in molecular imaging have transformed our ability to diagnose transthyretin cardiac amyloidosis noninvasively and unmasked a hitherto unrecognized prevalence of the disease. This review summarizes the current and evolving imaging approaches, their molecular structural basis, and the gaps in imaging capabilities that have arisen as a result of parallel developments in pharmacotherapy delivering the first effective treatment options for this condition.
Topics: Amyloidosis; Cardiomyopathies; Humans; Molecular Imaging
PubMed: 32482792
DOI: 10.2967/jnumed.120.245381 -
Molecules (Basel, Switzerland) Jul 2022The supersaturation of a solution refers to a non-equilibrium phase in which the solution is trapped in a soluble state, even though the solute's concentration is... (Review)
Review
The supersaturation of a solution refers to a non-equilibrium phase in which the solution is trapped in a soluble state, even though the solute's concentration is greater than its thermodynamic solubility. Upon breaking supersaturation, crystals form and the concentration of the solute decreases to its thermodynamic solubility. Soon after the discovery of the prion phenomena, it was recognized that prion disease transmission and propagation share some similarities with the process of crystallization. Subsequent studies exploring the structural and functional association between amyloid fibrils and amyloidoses solidified this paradigm. However, recent studies have not necessarily focused on supersaturation, possibly because of marked advancements in structural studies clarifying the atomic structures of amyloid fibrils. On the other hand, there is increasing evidence that supersaturation plays a critical role in the formation of amyloid fibrils and the onset of amyloidosis. Here, we review the recent evidence that supersaturation plays a role in linking unfolding/folding and amyloid fibril formation. We also introduce the HANABI (HANdai Amyloid Burst Inducer) system, which enables high-throughput analysis of amyloid fibril formation by the ultrasonication-triggered breakdown of supersaturation. In addition to structural studies, studies based on solubility and supersaturation are essential both to developing a comprehensive understanding of amyloid fibrils and their roles in amyloidosis, and to developing therapeutic strategies.
Topics: Amyloid; Amyloidosis; Humans; Solutions; Thermodynamics; beta 2-Microglobulin
PubMed: 35889461
DOI: 10.3390/molecules27144588 -
Acta Haematologica 2020
Topics: Amyloidosis; Disease Management; Humans; Treatment Outcome
PubMed: 32668431
DOI: 10.1159/000509736 -
Neurobiology of Aging May 2021Transgenic rodent models were created to decipher pathogenic mechanisms associated with Alzheimer's disease (AD), and behavioral apparatuses such as the Morris water...
Transgenic rodent models were created to decipher pathogenic mechanisms associated with Alzheimer's disease (AD), and behavioral apparatuses such as the Morris water maze (MWM) are used to assess cognition in mice. The IntelliCage was designed to circumvent issues of traditional behavioral tests, such as frequent human handling. The motivation to complete IntelliCage tasks is water consumption, which is less stressful than escaping from a pool in the MWM. Here, we examined behavioral performances of mice in the IntelliCage and MWM tasks. Twelve-month-old male and female APP/PS1 and non-transgenic mice first underwent 42 days of IntelliCage testing to assess prefrontal cortical and hippocampal function followed by MWM testing for six days. We found that females performed better in the IntelliCage while males performed superiorly in the MWM. Mechanistically, female APP/PS1 mice had a higher Amyloid-β plaque load throughout the brain, which is inconsistent with their performance in the IntelliCage. Collectively, these results inform scientists about the sex-based differences when testing animals in different behavioral paradigms that tap similar cognitive functions.
Topics: Amyloid beta-Peptides; Amyloidosis; Animals; Brain; Cognition; Disease Models, Animal; Female; Hippocampus; Humans; Male; Mice, Transgenic; Morris Water Maze Test; Motivation; Prefrontal Cortex; Sex Characteristics
PubMed: 33610962
DOI: 10.1016/j.neurobiolaging.2021.01.018 -
Methodist DeBakey Cardiovascular Journal 2022Amyloidosis is a disorder of protein misfolding and metabolism in which insoluble fibrils are deposited in various tissues, causing organ dysfunction and eventually... (Review)
Review
Amyloidosis is a disorder of protein misfolding and metabolism in which insoluble fibrils are deposited in various tissues, causing organ dysfunction and eventually death. Out of the 60-plus heterogeneous amyloidogenic proteins that have been identified, approximately 30 are associated with human disease. The unifying feature of these proteins is their tendency to form beta-pleated sheets aligned in an antiparallel fashion. These sheets then form rigid, nonbranching fibrils that resist proteolysis, causing mechanical disruption and local oxidative stress in affected organs such as the heart, liver, kidneys, nervous system, and gastrointestinal tract. Here we review the epidemiology of light chain amyloidosis, the staging, and the concomitant prognostication that is critical in determining the appropriate treatment.
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis
PubMed: 35414848
DOI: 10.14797/mdcvj.1070 -
Journal of the National Comprehensive... Jan 2023Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index... (Review)
Review
Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index of suspicion, making a delay in diagnosis common, which contributes to the high early mortality seen in this disease. Establishing the diagnosis of AL amyloidosis requires the demonstration of tissue deposition of amyloid fibrils. A bone marrow biopsy and fat pad aspirate performed concurrently have a high sensitivity for the diagnosis of AL amyloidosis and negate the need for organ biopsies in most patients. An accurate diagnosis requires amyloid typing via additional testing, including tissue mass spectrometry. Prognostication for AL amyloidosis is largely driven by the organs impacted. Cardiac involvement represents the single most important prognostic marker, and the existing staging systems are driven by cardiac biomarkers. Apart from organ involvement, plasma cell percentage on the bone marrow biopsy, specific fluorescence in situ hybridization findings, age at diagnosis, and performance status are important prognostic markers. This review elaborates on the diagnostic testing and prognostication for patients with newly diagnosed AL amyloidosis.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; In Situ Hybridization, Fluorescence; Plasma Cells; Risk Assessment
PubMed: 36630897
DOI: 10.6004/jnccn.2022.7077 -
Romanian Journal of Internal Medicine =... Mar 2023Transthyretin cardiac amyloidosis is a progressive disease known to cause heart failure, conduction anomalies, and arrythmias. Due to poor outcomes and mortality from... (Review)
Review
Transthyretin cardiac amyloidosis is a progressive disease known to cause heart failure, conduction anomalies, and arrythmias. Due to poor outcomes and mortality from severe cardiomyopathy, prevalence and incident rates are often underreported. As global longevity is increasing and rates of amyloidosis are also increasing, there is a need to improve diagnostic and therapeutic interventions. Previously, symptom management and transplantation were the mainstay of treatment for heart failure symptoms, but studies using RNAi and siRNA technologies have shifted the paradigm of therapeutic strategy in amyloid cardiomyopathy management. Additionally, early detection and clinical monitoring with numerous imaging and non-imaging techniques are being increasingly investigated. Here, we review the epidemiology, pathophysiology, diagnosis, and management of transthyretin amyloid cardiomyopathy.
Topics: Humans; Amyloidosis; Arrhythmias, Cardiac; Cardiomyopathies; Heart Failure; Prealbumin
PubMed: 36278951
DOI: 10.2478/rjim-2022-0018