In vitro and in vivo disease models of cardiac amyloidosis: progress, pitfalls, and potential

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Amyloid light chain (AL) and transthyretin amyloidosis (ATTR)-induced cardiomyopathy are life-threatening protein misfolding disorders characterized by amyloid fibril deposition in the heart, which significantly impairs cardiac function. The lack of representative disease models has impeded progress in understanding the underlying mechanisms and hindered the discovery and development of specific biomarkers and effective therapies. To address this, researchers have developed various cell and animal models to recapitulate these diseases. In AL amyloidosis, cell and mouse models have highlighted the toxic effects of both soluble light chains (LCs) and LC-derived amyloid fibrils, such as lysosomal dysfunction, endoplasmic reticulum stress, and oxidative stress. Transgenic mouse models, particularly those without the mouse heavy chain and with amyloid seeds addition, have successfully replicated systemic AL amyloidosis, with clear effects on the heart. For ATTR amyloidosis, acid-induced transthyretin (TTR) fibrils induce cellular dysfunction, such as increased intracellular reactive oxygen species (ROS) level, disorganized sarcomere, and prolonged calcium handling in 2D cell models. Transgenic mouse models expressing human WT or variant TTR have offered insights into the development of amyloid cardiomyopathy, but challenges persist in fully replicating the human phenotype. This revi

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

Browse all related research

Filter the research library by this study's title keywords, author, or publication year.