Database of articles cited by EMDB/PDB/SASBDB data

Keywords
Structure methods	All X-ray diffraction NMR electron microscopy small angle scattering neutron diffraction fiber diffraction powder diffraction infrared spectroscopy EPR fluorescence transfer theoretical model Hybrid
Author
Journal
IF	>30 >20 >10 >5 all

Title	Three-Dimensional Visualization and Proteomic Analysis of Human Cardiac Transthyretin Amyloidosis Tissue Reveals Microangiopathy and Capillary Occlusion.
Journal, issue, pages	J Am Heart Assoc, Vol. 15, Issue 10, Page e042248, Year 2026
Publish date	May 19, 2026
Authors	Joseph P Donnelly / Jan-Hannes Schäfer / Leonard Yoon / Lynée A Massey / Carl Ash / Zi Gao / Karina Nugroho / Marcus Jäger / Zhengyuan Pang / Robert T O'Neill / Mathew S Maurer / Evan T Powers / Gabriel C Lander / Li Ye / Jeffery W Kelly /
PubMed Abstract	BACKGROUND: Transthyretin amyloidosis (ATTR) is a degenerative disease affecting the heart and other organs. Transthyretin (TTR) aggregation is a driver of ATTR pathology, but the mechanism is poorly ...BACKGROUND: Transthyretin amyloidosis (ATTR) is a degenerative disease affecting the heart and other organs. Transthyretin (TTR) aggregation is a driver of ATTR pathology, but the mechanism is poorly understood. We used proteomics and tissue clearing technology on wild-type (WT) human cardiac (WT/WT) and V122I human cardiac (V122I/WT) tissue to better understand TTR cardiomyopathy. METHODS: Flash-frozen cardiac tissue slices from human subjects with end-stage WT-TTR cardiomyopathy, end-stage V122I TTR cardiomyopathy, and an age-matched control were used. Fibrils and tissue proteomes were extracted and assessed by bottom-up proteomics. Tissue clearing was performed using a lauryl sulfate-based lipid removal strategy. Slices were stained using indirect immunofluorescence against targets identified by proteomics. TTR deposits were imaged by antibody and AmyTracker 480 staining. Structures of ATTR fibrils were characterized using cryogenic electron microscopy. RESULTS: Proteomic analysis revealed high abundance of TTR, proteins associated with amyloid fibrils, as well as angiogenic, hemostatic, and complement cascade-associated proteins. Three-dimensional imaging revealed loss of normal microvascular architecture, regions of hypervascularization and hypovascularization, and microvascular obstruction by capillary thrombosis. ATTR fibrils adopted the spearhead fold and were decorated with collagen VI, an extracellular matrix component. CONCLUSIONS: Based on our imaging and proteomic data, we hypothesize that ATTR cardiomyopathy is a microangiopathy driven by capillary bed thromboinflammation and dysregulated angiogenic revascularization. In this model, increased capillary permeability exposes components of the vascular basement membrane to misfolded TTR. These components promote aggregation and stabilize amyloid fibrils. Congestion of the vascular basement membrane prevents appropriate revascularization, reducing cardiac exertional capacity over time, leading to heart failure.
External links	J Am Heart Assoc / PubMed:42089154
Methods	EM (helical sym.) / EM (single particle)
Resolution	3.0 - 9.7 Å
Structure data	71953 9px6 EMDB-71953, PDB-9px6: ATTR cardiac amyloid fibrils apex1 Method: EM (helical sym.) / Resolution: 3.2 Å 71960 9px7 EMDB-71960, PDB-9px7: ATTR cardiac amyloid fibrils apex2 Method: EM (helical sym.) / Resolution: 3.4 Å 71962 9px9 EMDB-71962, PDB-9px9: ATTR V122I cardiac amyloid fibrils Method: EM (helical sym.) / Resolution: 3.0 Å EMDB-73312: ATTR Collagen VI Cofibrils Method: EM (single particle) / Resolution: 5.3 Å EMDB-73313: Human Collagen VI microfibril Method: EM (single particle) / Resolution: 9.7 Å
Source	homo sapiens (human)
Keywords	PROTEIN FIBRIL / Transthyretin / amyloidosis