Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas; Department of Vascular Surgery, Changzheng Hospital, Second Military Medical University, Shanghai, China.
Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, Texas; Department of Cardiovascular Surgery, Texas Heart Institute, Houston, Texas.
J Surg Res. 2020 Jan;245:1-12. doi: 10.1016/j.jss.2019.07.013. Epub 2019 Aug 5.
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.
主动脉瘤和夹层形成过程中主动脉损伤、修复和重塑的机制尚不清楚。我们在散发性主动脉瘤和夹层的小鼠模型中研究了骨髓（BM）衍生细胞和固有主动脉细胞对主动脉损伤的反应。
野生型 C57BL/6 小鼠接受 GFP+BM 细胞移植。在 4 周内，这些小鼠接受普通饮食和生理盐水输注或高脂肪饮食和血管紧张素 II 输注。然后，我们检测了 GFP+BM 衍生细胞的招募、生长因子的产生以及 GFP+BM 衍生和 GFP-固有主动脉细胞的分化潜能。
主动脉损伤诱导 GFP+BM 细胞的招募和 GFP-固有主动脉细胞的激活，两者均产生生长因子。虽然 BM 细胞和固有主动脉细胞均能贡献成纤维细胞，但未检测到 BM 细胞向平滑肌细胞分化。有趣的是，主动脉巨噬细胞既有 BM 衍生的（45%）也有非 BM 衍生的（55%）来源。我们还观察到，在受挑战的小鼠的主动脉壁中，干细胞抗原-1（Sca-1）+干细胞/祖细胞和神经胶质抗原 2（NG2）+细胞数量显著增加。虽然一些 Sca-1+细胞和 NG2+细胞来源于 BM，但这些细胞大多是固有主动脉细胞。Sca-1+细胞产生生长因子并分化为成纤维细胞和 NG2+细胞。
BM 衍生和固有主动脉细胞在主动脉损伤时被激活，并通过产生生长因子和分化为成纤维细胞和炎症细胞来参与主动脉炎症、修复和重塑。
