Single-nucleus analysis of thoracic perivascular adipose tissue reveals critical changes in cell composition, communication, and gene regulatory networks induced by a high fat hypertensive diet.

Cardiovascular disease (CVD) is the leading cause of death worldwide, with hypertension being its primary causal factor. Most blood vessels are surrounded by perivascular adipose tissue (PVAT), which regulates blood vessel tone through the secretion of vasoactive factors. PVAT is recognized as a key mediator of vascular function and dysfunction in CVD, although the underlying mechanisms remain poorly understood. To investigate PVAT's mechanistic role in hypertension, we performed single nucleus RNA-Sequencing analysis of thoracic aortic PVAT from Dahl SS rats fed a high-fat, hypertensive diet. Computational analysis revealed extensive diet-induced changes in cell-type composition, cell-type specific gene expression, cell-cell communication pathways, and intracellular gene regulatory networks within PVAT. Furthermore, we identified key transcription factors mediating these networks and demonstrated through virtual knock-out experiments that these factors could serve as potential therapeutic targets for preventing or reversing PVAT's hypertensive state.