Fig. 3. RNA sequencing highlights cardiomyopathy, TGFβ, and cardiomyocyte dysfunction pathways in Adamtsl3 knock-out hearts in response to pressure overload.

Pressure overload of the left ventricle (LV) was induced in Adamtsl3 knock-out (L3-KO, n = 10) and wild-type (WT, n = 6) mice by aortic banding (AB) for 1 week, and RNA sequencing was performed on LV tissue. 233 differentially expressed genes (DEGs, FDR < 0.05) were analysed for enrichment of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways and Gene Ontology (GO) terms using Database for Annotation, Visualization and Integrated Discovery (DAVID) v6.8 analysis wizard⁴⁹. The 10 most enriched a KEGG pathways, b GO biological pathways, c GO molecular functions, and d GO cellular components, identified among the 233 DEGs are shown. e Scatterplot comparing log reads per kilobase million (RPKM) of 233 DEGs between L3-KO and WT. Red dots correspond to annotated DEGs in the graph. The complete list of DEGs (gray and red dots) can be found in Supplementary Data 1. f-g Log2-fold change of mean RPKM of DEGs related to cardiomyocyte (CM) structure and function (f), and extracellular matrix (ECM) and cardiac fibrosis (g). h-i Predicted upstream regulators of DEGs from Ingenuity Pathway Analysis (IPA).