3D Visualization and Proteomic Analysis of Human Cardiac Transthyretin Amyloidosis Tissue Reveals Microangiopathy and Capillary Occlusion.

ABSTRACT:

Background

Transthyretin amyloidosis (ATTR) is a progressive, degenerative disease affecting the heart and other organ systems, as well as the peripheral, autonomic, and central nervous systems. Although pharmacological and genetic evidence establishes aggregation as a driver of ATTR pathology, the mechanism by which aggregation compromises post-mitotic tissue function is poorly understood. We utilized bottom-up proteomics on wild-type (WT) human cardiac (WT/WT genotype) and V122I human cardiac (V122I/WT genotype) tissue, combined with tissue clearing technology to create an optically transparent tissue architecture to visualize three-dimensional relationships, to better understand TTR cardiomyopathy (CM).

Methods

Flash-frozen 0.5 mm cardiac tissue slices from human subjects

SUBMITTER: Donnelly JP 

PROVIDER: S-EPMC12918892 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature