Abstract
Hypertension drives heterogeneous aortic remodeling, but the mechanisms underlying regional disparities remain unclear. Here, we demonstrate that adaptive immunity orchestrates spatial differences in vascular dysfunction by modulating perivascular adipose tissue (PVAT) phenotype and immune-metabolic crosstalk. Using angiotensin II (AngII)-infused wild-type (WT) and Rag1 (-/-) mice lacking T and B cells, we integrated biaxial mechanical testing, bulk transcriptomics, and PVAT analyses. In WT mice, AngII induced pronounced descending thoracic aorta (DTA) remodeling, marked by wall thickening, reduced circumferential stiffness and inflammatory gene upregulation ( Il6 , Ccl2 ). These changes were attenuated in Rag1 (-/-) mice, implicating T cells in thoracic maladaptation. Conversely, the infrarenal abdominal aorta (IAA) exhibited hypertensive resilience in WT mice but unmasked PPARγ-associated metabolic reprogramming ( Pparg , Adipoq ) in Rag1 (-/-) mice, suggesting T cells suppress protective abdominal adaptations. PVAT heterogeneity emerged as a key regulator wherein thoracic PVAT (T-PVAT) adopted a pro-inflammatory phenotype (CCL5, TIMP-1) in WT mice, exacerbating DTA damage, while Rag1 (-/-) mice showed thermogenic plasticity ( Ucp1 upregulation) in abdominal PVAT (A-PVAT). T cell reconstitution restored maladaptive remodeling in Rag1 (-/-) mice, confirming adaptive immunity's dual role in promoting thoracic injury and restraining metabolic resilience. This work identifies PVAT as an immune-metabolic switch governing regional susceptibility to vascular remodeling, offering spatially resolved strategies to preserve aortic compliance in hypertensive disease.