摘要：SummaryTo identify cellular mechanisms responsible for pressure overload triggered heart failure, we isolated cardiomyocytes, endothelial cells, and fibroblasts as most abundant cell types from mouse hearts in the subacute and chronic stages after transverse aortic constriction (TAC) and performed RNA-sequencing. We detected highly cell-type specific transcriptional responses with characteristic time courses and active intercellular communication. Cardiomyocytes after TAC exerted an early and sustained upregulation of inflammatory and matrix genes and a concomitant suppression of metabolic and ion channel genes. Fibroblasts, in contrast, showed transient early upregulation of inflammatory and matrix genes and downregulation of angiogenesis genes, but sustained induction of cell cycle and ion channel genes during TAC. Endothelial cells transiently induced cell cycle and extracellular matrix genes early after TAC, but exerted a long-lasting upregulation of inflammatory genes. As we found that matrix production by multiple cell types triggers pathological cellular responses, it might serve as a future therapeutic target.Graphical abstractDisplay OmittedHighlights•TAC induces matrix and growth, but reduces contraction genes in cardiomyocytes•TAC induces genes related to matrix, inflammation, and cell cycle in endothelial cells•TAC induces matrix and inflammation, but reduces angiogenesis genes in fibroblasts•Matrix proteins trigger growth, proliferation, and migration in cardiac cellsBiological sciences; Molecular biology; Systems biology; Transcriptomics
