Background <p>Hypertension-associated aortic dissection (HTN-AD) features intense immune activation and extracellular matrix disruption, yet the cellular programs that promote aortic-wall stabilization remain unclear. We aimed to identify macrophage states associated with vascular integrity and to determine whether these states could be mechanistically or therapeutically leveraged.</p> Methods <p>Single-cell RNA sequencing was performed on thoracic aortas from HTN-AD, Marfan syndrome-associated AD, and donor controls (<i>n</i> = 3 per group). Peripheral and tear-adjacent blood samples were analyzed in patients with HTN-AD, MS-AD, and healthy donors (<i>n</i> = 30 per group), with paired intraoperative tear-adjacent sampling performed when available (<i>n</i> = 10). Circulating monocytes and serum cytokines were profiled by flow cytometry and ELISA. Functional validation included TGF-β1 conditioning of human monocytes and murine macrophages and adoptive transfer experiments in a murine AD model.</p> Results <p>A distinct SPP1^high fibrogenic macrophage population was enriched in diseased aortas and transcriptionally bridged low-inflammatory macrophages and matrix-active states. Patients with HTN-AD displayed increased tear-adjacent non-classical monocytes and higher monocytic SPP1, correlating with serum TGF-β1 and a shorter ICU stay. TGF-β1 induced an SPP1-dependent fibrogenic program in macrophages while suppressing inflammatory markers. Myeloid Spp1 deficiency aggravated aortic dilatation and wall disruption, whereas adoptive transfer of TGF-β1-conditioned SPP1^high macrophages reduced false lumen formation, improved collagen organization, decreased IL-1β and IL-6 expression, and enhanced survival.</p> Conclusions <p>A TGF-β1–SPP1 axis drives the emergence of SPP1^high fibrogenic macrophages that support structural stabilization of the dissected aorta. Targeting this reparative myeloid program may offer a mechanistically informed therapeutic strategy for acute aortic syndromes.</p> Graphical Abstract <p></p>