Activation of Bone Marrow–Derived Cells and Resident Aortic Cells During Aortic Injury

• Published in: The Journal of surgical research 2020-01, Vol.245, p.1-12
• Main Authors: Zou, Sili, Ren, Pingping, Zhang, Lin, Azares, Alon R., Zhang, Sui, Coselli, Joseph S., Shen, Ying H., LeMaire, Scott A.
• Format: Article
• Language: English
• Subjects: Aneurysm, Dissecting - etiology; Aneurysm, Dissecting - immunology; Aneurysm, Dissecting - pathology; Animals; Aorta - cytology; Aorta - immunology; Aorta - pathology; Aortic aneurysm; Aortic Aneurysm - complications; Aortic Aneurysm - pathology; Bone marrow cells; Cell Differentiation - immunology; Disease Models, Animal; Fibroblasts - immunology; Fibroblasts - metabolism; Hematopoietic Stem Cells - immunology; Hematopoietic Stem Cells - metabolism; Humans; Intercellular Signaling Peptides and Proteins - metabolism; Macrophages - immunology; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Myocytes, Smooth Muscle - immunology; Myocytes, Smooth Muscle - metabolism
• ISSN: 0022-4804; 1095-8673
• DOI: 10.1016/j.jss.2019.07.013

The process of aortic injury, repair, and remodeling during aortic aneurysm and dissection is poorly understood. We examined the activation of bone marrow (BM)-derived and resident aortic cells in response to aortic injury in a mouse model of sporadic aortic aneurysm and dissection. Wild-type C57BL/6 mice were transplanted with green fluorescent protein (GFP)+ BM cells. For 4 wk, these mice were either unchallenged with chow diet and saline infusion or challenged with high-fat diet and angiotensin II infusion. We then examined the aortic recruitment of GFP+ BM-derived cells, growth factor production, and the differentiation potential of GFP+ BM-derived and GFP− resident aortic cells. Aortic challenge induced recruitment of GFP+ BM cells and activation of GFP− resident aortic cells, both of which produced growth factors. Although BM cells and resident aortic cells equally contributed to the fibroblast populations, we did not detect the differentiation of BM cells into smooth muscle cells. Interestingly, aortic macrophages were both of BM-derived (45%) and of non−BM-derived (55%) origin. We also observed a significant increase in stem cell antigen-1 (Sca-1)+ stem/progenitor cells and neural/glial antigen 2 (NG2+) cells in the aortic wall of challenged mice. Although some of the Sca-1+ cells and NG2+ cells were BM derived, most of these cells were resident aortic cells. Sca-1+ cells produced growth factors and differentiated into fibroblasts and NG2+ cells. BM-derived and resident aortic cells are activated in response to aortic injury and contribute to aortic inflammation, repair, and remodeling by producing growth factors and differentiating into fibroblasts and inflammatory cells.