Pfaltzgraff Elise R, Shelton Elaine L, Galindo Cristi L, Nelms Brian L, Hooper Christopher W, Poole Stanley D, Labosky Patricia A, Bader David M, Reese Jeff
Department of Cell and Developmental Biology, Vanderbilt University, 2220 Pierce Ave, PRB 348, Nashville, TN 37232, USA.
Department of Pediatrics, Vanderbilt University, 2215 B Garland Ave., 1125 MRB IV Bldg, Nashville, TN 37232, USA.
J Mol Cell Cardiol. 2014 Apr;69:88-96. doi: 10.1016/j.yjmcc.2014.01.016. Epub 2014 Feb 4.
Vascular smooth muscle cells (VSMCs) are derived from distinct embryonic origins. Vessels originating from differing smooth muscle cell populations have distinct vascular and pathological properties involving calcification, atherosclerosis, and structural defects such as aneurysm and coarctation. We hypothesized that domains within a single vessel, such as the aorta, vary in phenotype based on embryonic origin. Gene profiling and myographic analyses demonstrated that embryonic ascending and descending aortic domains exhibited distinct phenotypes. In vitro analyses demonstrated that VSMCs from each region were dissimilar in terms of cytoskeletal and migratory properties, and retention of different gene expression patterns. Using the same analysis, we found that these same two domains are indistinguishable in the adult vessel. Our data demonstrate that VSMCs from different embryonic origins are functionally distinct in the embryonic mouse, but converge to assume a common phenotype in the aorta of healthy adults. These findings have fundamental implications for aortic development, function and disease progression.
血管平滑肌细胞(VSMCs)起源于不同的胚胎来源。源自不同平滑肌细胞群体的血管具有不同的血管和病理特性,包括钙化、动脉粥样硬化以及诸如动脉瘤和缩窄等结构缺陷。我们推测,在单个血管(如主动脉)内的区域,其表型会因胚胎起源而有所不同。基因谱分析和肌电图分析表明,胚胎期升主动脉和降主动脉区域表现出不同的表型。体外分析表明,来自每个区域的血管平滑肌细胞在细胞骨架和迁移特性以及不同基因表达模式的保留方面存在差异。通过相同的分析,我们发现这两个相同的区域在成年血管中难以区分。我们的数据表明,来自不同胚胎起源的血管平滑肌细胞在胚胎小鼠中功能不同,但在健康成年小鼠的主动脉中会趋同以呈现共同的表型。这些发现对主动脉的发育、功能和疾病进展具有重要意义。