Authors: Rahul Sehgal
Published: 2023-10-13
DOI: 10.1161/res.133.suppl_1.p2012
Source: Full article
The borderzone (BZ) of the infarcted heart separates poorly-perfused areas of cell death from well-perfused territories of comparatively normal myocardium. The BZ after myocardial infarction is of key importance for the remodeling process that drives heart failure and sudden cardiac death. We recently defined the transcriptional features of the infarct borderzone using single cell RNA-Seq and spatial transcriptomics which revealed prominent upregulation of mechanotransduction transcriptional programs. A similar transcriptional response was inducible by needle trauma alone. To explain these results, we proposed the “Loss of Neighbor” (LON) Hypothesis, where surviving cells neighboring the infarct experience mechanical instability due to the highly asymmetric loss of load, leading to cell signal activation. Here, we develop and validate an