Investigating pathology associated with cardiac hypertrophy at the single-cell level

Importantly, 19 genes were consistently dysregulated across all models, suggesting a common link to CH regardless of the pathological stimulus. These candidate genes are novel or poorly characterised in the context of pathological CH.<br><br>After devising a bioinformatic technique to systematically assess conservation in mouse-human cardiac gene expression, dysregulated expression was characterised at the single-cell level in human heart samples from hypertensive disease patients.

This represents a novel study of human HTD, identifying prominent changes in gene expression and possible alterations in cardiac tissue composition in HTD, a condition which is responsible for most cases of pathological CH in humans. Of the 19 candidate genes implicated in CH via mouse models, 15 were also dysregulated in human HTD versus normal heart. These 15 genes (ADAMTS4, ADAMTS9, AKAP12, B2M, B4GALT5, CMSS1, DENND4A, EMP1, FOSL2, JUN, KLF2, NFKBIZ, PDE4B, UBASH3B, and ZBTB16) are hypothesised to include key drivers of cardiac hypertrophy under pathological stimulus, a characterisation which is either novel or under-appreciated for each of the 15 candidates.<br><br><i>Thesis is embargoed until 31 July 2030.</i>