GAUTHIER, J. | bioRxiv Science

bioRxiv2024

LSD1 demethylase inhibition prevents cardiac fibrosis in both ischemic and congenital diseases in mice and pig models

Fibrosis is part of a clinical burden in cardiovascular diseases. The pathological process has been the subject of intensive research with still mitigated therapeutic options. Recently chromatin modifiers have turned out to be potential drugs to modulate fibrosis. Here, in order to address the question of pharmacological inhibition of fibrosis, we used both a mouse model of myocardial infarction with left ventricular fibrosis and a more clinically relevant pig model of right ventricular failure featuring interstitial fibrosis. Treatment of these diseased animal models with an inhibitor of the Lysine Demethylase 1 (LSD1) significantly prevented both left and right ventricular failure in both the mouse and the pig, respectively. This was revealed by a significant recovery of left ventricular function post-myocardial infarction in the mouse and a limitation of remodeling of the pig right ventricle, thus preserving its function. Fibrosis was significantly decreased in both mouse and pig hearts, which likely account for improvement in ventricular function. We thus provide evidence of the beneficial effect of LSD1 inhibitors in cardiac fibrosis and of the use of such drugs to preserve ventricular function in both ischemic and congenital heart diseases. NEW & NOTEWORTHYDrugs to prevent cardiac fibrosis has been the subject of intensive research with limited outcomes. This work inspired by oncology, provides evidence that an epigenetic modifier which targets the process of epithelial-to-mesenchymal transition turns out to be an efficient inhibitor of fibrosis for both ischemic and non-ischemic myocardial diseases.

pharmacology and toxicology↗

bioRxiv2024

Museomics of Carabus giant ground beetles evidences an Oligocene origin and in situ Alpine diversification

The development of museomics represents a major paradigm shift in the use of natural history collection specimens for systematics and evolutionary biology. New approaches in this field allow the sequencing of hundreds to thousands of loci from across the genome using historical DNA. HyRAD-X, a recently introduced capture method using bench-top designed probes, has proved very efficient for recovering genomic-scale datasets using natural history collection specimens. Using this technique at both the intra- and interspecific levels, we infer the most robust phylogeny to date for Arcifera, an ecologically and morphologically diverse clade of Carabus giant ground beetles. We successfully generated a genomic dataset of up to 1965 HyRAD-X loci for all described species, permitting inference of a robust dated phylogenomic tree for this clade. Our species delimitation and population genomic analyses suggest that the current classification for Arcifera is in line with its evolutionary history. Our results suggest an origin of Arcifera in the late Oligocene followed by speciation events during the warm mid-Miocene unlinked to Pleistocene glaciations. The dynamic paleogeographic history of the Palearctic region likely contributed to the diversification of this lineage with a relatively ancient colonization of the proto-Alps followed by in situ speciation where most species of Arcifera are currently found sometimes syntopically likely as a result of post-glaciations secondary contacts.

zoology↗