Sawada Hisashi, Rateri Debra L, Moorleghen Jessica J, Majesky Mark W, Daugherty Alan
From the Saha Cardiovascular Research Center (H.S., D.L.R., J.J.M., A.D.) and Department of Physiology (A.D.), University of Kentucky, Lexington; Seattle Children's Research Institute, Washington (M.W.M.); and Department of Pediatrics and Department of Pathology, University of Washington, Seattle (M.W.M.).
Arterioscler Thromb Vasc Biol. 2017 Sep;37(9):1722-1726. doi: 10.1161/ATVBAHA.117.309599. Epub 2017 Jun 29.
Smooth muscle cells (SMCs) of the proximal thoracic aorta are embryonically derived from the second heart field (SHF) and cardiac neural crest (CNC). However, distributions of these embryonic origins are not fully defined. The regional distribution of SMCs of different origins is speculated to cause region-specific aortopathies. Therefore, the aim of this study was to determine the distribution of SMCs of SHF and CNC origins in the proximal thoracic aorta.
Mice with repressed LacZ in the ROSA26 locus were bred to those expressing controlled by either the Wnt1 or Mef2c (myocyte-specific enhancer factor 2c) promoter to trace CNC- and SHF-derived SMCs, respectively. Thoracic aortas were harvested, and activity of β-galactosidase was determined. Aortas from Wnt1- mice had β-galactosidase-positive areas throughout the region from the proximal ascending aorta to just distal of the subclavian arterial branch. Unexpectedly, β-galactosidase-positive areas in Mef2c- mice extended from the aortic root throughout the ascending aorta. This distribution occurred independent of sex and aging. Cross and sagittal aortic sections demonstrated that CNC-derived cells populated the inner medial aspect of the anterior region of the ascending aorta and transmurally in the media of the posterior region. Interestingly, outer medial cells throughout anterior and posterior ascending aortas were derived from the SHF. β-Galactosidase-positive medial cells of both origins colocalized with an SMC marker, α-actin.
Both CNC- and SHF-derived SMCs populate the media throughout the ascending aorta. The outer medial cells of the ascending aorta form a sleeve populated by SHF-derived SMCs.
胸主动脉近端的平滑肌细胞(SMC)在胚胎期起源于第二心脏场(SHF)和心脏神经嵴(CNC)。然而,这些胚胎起源的分布尚未完全明确。推测不同起源的SMC的区域分布会导致区域特异性主动脉病变。因此,本研究的目的是确定胸主动脉近端中源自SHF和CNC的SMC的分布。
将ROSA26位点中LacZ受抑制的小鼠与分别由Wnt1或Mef2c(肌细胞特异性增强因子2c)启动子控制表达的小鼠进行杂交,以分别追踪源自CNC和SHF的SMC。采集胸主动脉,并测定β-半乳糖苷酶的活性。来自Wnt1-小鼠的主动脉在从升主动脉近端到锁骨下动脉分支远端的整个区域都有β-半乳糖苷酶阳性区域。出乎意料的是,Mef2c-小鼠中的β-半乳糖苷酶阳性区域从主动脉根部延伸至整个升主动脉。这种分布与性别和年龄无关。主动脉的横切面和矢状切面显示,源自CNC的细胞分布在升主动脉前部区域的内侧,在后壁区域的中膜呈透壁性分布。有趣的是,升主动脉前后部的外侧中膜细胞均源自SHF。两种起源的β-半乳糖苷酶阳性中膜细胞均与SMC标志物α-肌动蛋白共定位。
源自CNC和SHF的SMC均分布于整个升主动脉的中膜。升主动脉的外侧中膜细胞形成一个由源自SHF的SMC组成的套层。