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AimsThe proteasome prevents the intracellular accumulation of proteins and its impairment can lead to structural and functional alterations, as noted for the coronary vasculature in a previous study. Utilizing the same model, this study was designed to test the hypothesis that chronic proteasome inhibition (PSI) also leads to structural and functional changes of the heart. Methods and resultsFemale domestic pigs were randomized to a normal diet without (N) or with twice-weekly subcutaneous injections of the proteasome inhibitor MLN-273 (0.08 mg/kg, N + PSI, n ¼ 5 each group). In vivo data on cardiac structure and function as well as myocardial perfusion and microvascular permeability response to adenosine and dobutamine were obtained by electron beam computed tomography after 11 weeks. Subsequent ex vivo myocardial analyses included immunoblotting, immunostaining, TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labelling), Masson trichrome, and Congo red staining. Compared with N, an increase in LV mass was observed in N + PSI (106.5 + 16.4 g vs. 183.1 + 24.2 g, P , 0.05). The early to late diastolic filling ratio was increased in N + PSI vs. N (3.5 + 0.6 vs. 1.8 + 0.1, P , 0.05). The EF tended to be lower (46 + 12% and 53 + 9%, respectively) and cardiac output was significantly lower in N + PSI than in N (2.9 + 1.1 vs. 4.7 + 1.1 L/min, P , 0.05). Tissue analyses demonstrated an accumulation of proteasome substrates, apoptosis, and fibrosis in the PSI group. Compared with N, the myocardial perfusion response was reduced and microvascular permeability was increased in N + PSI. ConclusionThe current study demonstrates that chronic proeasome inhibition affects the cardiovascular system, leading to functional and structural alteration of the heart consistent with a hypertrophic-restrictive cardiomyopathy phenotype.--

The social amoeba Dictyostelium discoideum has long served as a model system for studying fundamental processes in cell and developmental biology. This eukaryotic microbe is also recognized as a model organism for biomedical and human disease research since the genome encodes homologs of genes linked to human disease, such as those linked to cancer and neurodegeneration. Dictyostelium has a unique life cycle composed of a unicellular growth phase and a multicellular developmental phase that is induced by starvation. During its life cycle, Dictyostelium undergoes conserved cellular processes including, but not limited to, cell proliferation, phagocytosis, intercellular signaling, cell adhesion and motility, chemotaxis, and cell differentiation. The history of the organism, the resources available to researchers in the community, and the diverse ways that Dictyostelium is used in the contemporary research lab are discussed. © 2017 by John Wiley & Sons, Inc.

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