Abdominal aortic aneurysms (AAA) are the most common subtype of aortic aneurysms and share several etiological mechanisms with thoracic aortic aneurysms (TAA), which involve the aortic root, ascending aorta, arch, or descending thoracic segment. Despite these similarities, AAA and TAA differ markedly in their hemodynamic properties, extracellular matrix composition, and inflammatory profiles. While inflammation is a well-established driver of matrix degradation in AAA, its contribution to TAA formation remains less clear. Aneurysm development depends on hematopoietic activity supplying immune and inflammatory cells that promote vascular remodeling. For a long time, hematopoietic studies focused primarly on the long bones. Owing to their close anatomical proximity to the aorta, vertebral bone marrow (BM) may represent another spatially linked and active hematopoietic niche influencing local vascular inflammation. Yet, it remains unknown whether this proximity promotes region-specific hematopoietic activation and whether such locoregional responses are particularly relevant during early aneurysm formation.
The present study aimed to analyze locoregional hematopoietic responses in distinct hematopoietically active BM compartments during aortic aneurysm development. Male C57BL/6J mice (8–12 weeks) were treated with angiotensin II (AngII, 1000 ng/kg/min) and β-aminopropionitrile (BAPN, 0.1% in drinking water) to induce TAA and AAA. Aneurysms were assessed by ultrasound, magnetic resonance imaging (MRI), invasive blood pressure measurement, and histological and flow cytometric analyses of BM and aortic tissue. mRNA expression of Csf2r, Cxcr2, Mcp1, and Tnf was analyzed in BM-derived leukocytes by qPCR, and RNA sequencing of endothelial cells was performed during early aneurysm formation.
Treatment with AngII/BAPN resulted in TAA in 30%, AAA in 20%, and combined TAA and AAA in 42% of mice, while 8% did not develop aneurysms. Thoracic ruptures were more frequent than abdominal ones. Blood pressure increased rapidly within the first day of AngII exposure. After one day of treatment, thoracic aortae were already enlarged compared to controls. Leukocytes from thoracic vertebrae showed altered Csf2r and TNF expression, indicating early activation of differentiation and inflammatory pathways. Flow cytometry revealed a marked inflammatory response in vertebral BM only after four days, whereas long bones showed no such activation, suggesting a locoregional hematopoietic response in the vertebrae. Histological analyses after 28 days confirmed increased mononuclear cell numbers in the vascular niche of vertebral bodies.
In conclusion, these findings demonstrate a spatially restricted hematopoietic activation during early stages of aortic aneurysm development, highlighting the functional coupling between the aorta and adjacent vertebral BM compartments.
