Locoregional Immune Response in Thoracic and Abdominal Aortic Aneurysms

Abdominal aortic aneurysms (AAA) are the most common form of aortic aneurysms, and share etiological similarities with thoracic aortic aneurysms (TAA) which occur in the thoracic aorta including the aortic root, ascending aorta, aortic arch and descending aorta. However, AAA and TAA differ in their hemodynamic properties, differences in the composition of the extracellular matrix of the vascular wall and the inflammatory response. While inflammation is a well described process in matrix degradation in AAA, its importance for TAA still remains elusive. Inflammation in aneurysm development depends on an increased haematopoietic activity. Here, the long bones play an important role in haematopoiesis in early childhood, however, their capacity decreases with age. Thus, in adults, haematopoiesis occurs mainly in the sternum and vertebral bodies, with the vertebral bodies being particularly close to the aorta and thus to aneurysms. Yet it is not clear whether the locoregional proximity of the bone marrow to the site inflammation is decisive for activation of specific hematopoietic active compartments.

Thus, aim of the current study was to analyse the locoregional haematopoietic responses in different bone marrow niches during the development of aortic aneurysms.

The model of combined application of angiotensin II (Ang-II, 1000 ng/kg/min) and β-Aminopropionitril (BAPN, 0,1 % in drinking water) was used for studying TAA and AAA in male 8-12 week old C57BL/6J mice. Aneurysms were investigated using magnetic resonance imaging (MRI), ultrasound, histological and flow cytometric analysis of bone marrow and abdominal/thoracic aorta, mRNA expression analysis of Csf2r and Cxcr2 by qPCR, and enzyme-linked immunosorbent assay for detection of stromal cell derived factor (SDF) 1.

Treatment with Ang-II/BAPN resulted in TAA in 30 % of the treated mice, AAA in 20 % and TAA and AAA in 42 %, while 8 % did not develop an aneurysm. More mice died due to ruptures of the thoracic aorta than from ruptures of the abdominal aorta, which indicates a lower stability of the thoracic vessel walls. 19F MRI revealed a locoregional immune response in developing aortic aneurysms as well as the in vertebral bodies near those incipient aneurysms. This locoregional activation was confirmed by flow cytometry revealing an increased inflammatory response in vertebrae in close vicinity to the aneurysm. In line, histological staining confirmed more mononuclear cells in the vascular niche of these locally activated vertebral bodies. Further, increased amounts of SDF1 were detected in vertebral bodies in aneurysm proximity thereby promoting immune cell migration from the endosteal to the vascular niche. 

Our results underscore the critical role of locoregional differences occuring during the development of thoracic and abdominal aortic aneurysms.