Pauza, A. G. | bioRxiv Science

bioRxiv2022

Multiomic deep delve of synthesis and secretion processes in a model peptidergic system

The cell bodies of hypothalamic magnocellular neurones are densely packed in the hypothalamic supraoptic nucleus (SON) whereas their axons project to the anatomically discrete posterior pituitary gland. We have taken advantage of this unique anatomical structure to establish proteome and phosphoproteome dynamics in neuronal cell bodies and axonal terminals in response to physiological stimulation. We have found that proteome and phosphoproteome responses are very different between somatic and axonal neuronal compartments, indicating the need of each cell domain to differentially adapt. In particular, changes in the phosphoproteome in the cell body are involved in the reorganisation of the cytoskeleton and in axonal terminals the regulation of synaptic and secretory processes. We have identified that prohormone precursors including vasopressin and oxytocin are phosphorylated in axonal terminals and become hyperphosphorylated following stimulation. By multi-omic integration of transcriptome and proteomic data we identify changes to proteins present in afferent inputs to this nucleus. Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=152 SRC="FIGDIR/small/494122v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@adc36org.highwire.dtl.DTLVardef@ff7d0corg.highwire.dtl.DTLVardef@16abd16org.highwire.dtl.DTLVardef@a41e3d_HPS_FORMAT_FIGEXP M_FIG C_FIG

neuroscience↗

bioRxiv2022

Reproducing extracellular matrix adverse remodelling of non-ST myocardialinfarction in a large animal model

The rising incidence of non-ST-segment elevation myocardial infarction (NSTEMI) and associated long-term high mortality constitutes an urgent clinical issue. Unfortunately, the study of possible interventions to treat this pathology lacks a reproducible pre-clinical model. Indeed, currently adopted small and large animal models of MI mimic only full-thickness, ST-segment-elevation (STEMI) infarcts, and hence cater only for investigation into therapeutics and interventions directed at this subset of MI. Thus, we developed an ovine model of NSTEMI by ligating the myocardial muscle at precise intervals parallel to the left anterior descending coronary artery. After validating the presented model both by histology and functional analysis with clinical data, further omics analyses highlighted the distinctive features of post-NSTEMI tissue remodelling. Here, by looking at the transcriptome and proteome-derived pathways emerging at acute (7 days) and late (28 days) post-surgery timepoints, we discovered specific alterations in cardiac post-ischaemic extracellular matrix (ECM). Together with the rise of well-known markers of inflammation and fibrosis, NSTEMI ischaemic regions showed distinctive patterns in the expression of complex N-glycans and glycosaminoglycans in cellular membranes and ECM. Identifying such changes in molecular moieties accessible to infusible and intra-myocardial injectable drugs sheds light on the development of targeted pharmacological solutions to contrast adverse fibrotic remodelling.

bioengineering↗