Patterns of coronary vascular involvement in patients with heart failure due to cardiac amyloidosis

Background Amyloidosis is a group of protein-folding disorders characterised by organ deposits, derived from one of several amyloidogenic precursor proteins. The involvement of coronary arteries has been previously described in amyloidosis, however the pattern of the disease in the coronaries is still unknown. Purpose The aim of this study is to characterise the pattern and severity of coronary artery lesions in cardiac amyloidosis. Methods We retrospectively compared patients with heart failure who tested positive (i.e. biopsy or gene tests – HF/CA+) against those that tested negative (HF/CA−) for cardiac amyloidosis. Groups were compared demographically and angiographically for qualitative and quantitative variables to determine patterns of involvement in the major epicardial coronary vessels. Results In total, 110 heart failure patients were included in the study, of whom 55 were HF/CA+ patients (88 lesions) and 55 were HF/CA− patients (66 lesions). Despite the advanced age in the HF/CA+, (74.53±11.02 vs 54.11±15.08; p=0.05), severe calcification was reported in HF/CA− group (4.5% vs to 0.0%; p=0.018). The HF/CA+ group also had fewer ostial lesions (3.4% vs. 15.15%, p=0.0095), reduced TIMI flow grade (83% vs 76%; p=0.21) and a higher TIMI frame count (30±12 Vs 27±11 frames; p=0.06). In the HF/CA+ group, compared to women, men had a significant number of tandem lesions (14.55% vs 0.0%, p=0.02). Men trended to have more ulcerations in comparison to women (9.09% vs 0.0%; p=0.15). Conclusion Overall, patients with HF/CA+ were older but found to have lesser calcified lesions, ostial involvement and a reduced anterograde blood flow. This is the first report outlining the coronary lesions in patients with HF/CA+. Funding Acknowledgement Type of funding source: None

Cadmium Causes Misfolding and Aggregation of Cytosolic Proteins in Yeast

ABSTRACT Cadmium is a highly poisonous metal and is classified as a human carcinogen. While its toxicity is undisputed, the underlying in vivo molecular mechanisms are not fully understood. Here, we demonstrate that cadmium induces aggregation of cytosolic proteins in living Saccharomyces cerevisiae cells. Cadmium primarily targets proteins in the process of synthesis or folding, probably by interacting with exposed thiol groups in not-yet-folded proteins. On the basis of in vitro and in vivo data, we show that cadmium-aggregated proteins form seeds that increase the misfolding of other proteins. Cells that cannot efficiently protect the proteome from cadmium-induced aggregation or clear the cytosol of protein aggregates are sensitized to cadmium. Thus, protein aggregation may contribute to cadmium toxicity. This is the first report on how cadmium causes misfolding and aggregation of cytosolic proteins in vivo. The proposed mechanism might explain not only the molecular basis of the toxic effects of cadmium but also the suggested role of this poisonous metal in the pathogenesis of certain protein-folding disorders.