Mikawa T, Gourdie R G
Department of Cell Biology and Anatomy, Cornell University Medical College, New York, NY 10021, USA.
Dev Biol. 1996 Mar 15;174(2):221-32. doi: 10.1006/dbio.1996.0068.
The vascular smooth muscle cells of coronary arteries are distinguished from those of the proximal aorta by a number of structural and functional criteria which may include an increased propensity for atherosclerotic transformation. At present, the source of this variation between smooth muscle subpopulations is uncertain. Whilst smooth muscle of the proximal aorta is thought to be derived from neural crest, the origin of coronary vascular smooth muscle remains uncharacterized. We have previously shown that precursors of the coronary vasculature enter the tubular heart on the same day as the epicardial mantle starts to envelop the myocardium and that coronary vessels form by ingrowth of these migratory precursors and not by outgrowth from the aorta (Mikawa and Fischman, 1992). To study the origin of coronary smooth muscle cells, the proepicardial organ, from which epicardial cells arise, was tagged with either a vital dye (DiI) or replication-defective retroviruses encoding beta-galactosidase. Cellular lineage marking was achieved by either direct targeting of putative vasculogenic cells in the proepicardium in ovo or tagging dissected proepicardial cells in vitro followed by transplantation to stage-matched host embryos. Monitoring of tagged cells during coronary vasculogenesis indicate incorporation of proepicardial-derived cells into three vessel-associated populations; coronary smooth muscle, perivascular connective tissue, and endothelial cells. Immunoconfocal microscopy identified both endothelial and smooth muscle cell populations within the proepicardial organ. The results demonstrate that: (1) the proepicardium contains a progenitor population of coronary smooth muscle cells that migrates into the heart along with ingrowth of the epicardium and (2) prior to the migration, the coronary smooth muscle lineage is established.
冠状动脉的血管平滑肌细胞在结构和功能标准方面与近端主动脉的血管平滑肌细胞有所不同，这些标准可能包括动脉粥样硬化转变倾向增加。目前，平滑肌亚群之间这种差异的来源尚不确定。虽然近端主动脉的平滑肌被认为起源于神经嵴，但冠状血管平滑肌的起源仍未明确。我们之前已经表明，冠状血管的前体细胞在脏层心包开始包裹心肌的同一天进入管状心脏，并且冠状血管是由这些迁移的前体细胞向内生长形成的，而不是从主动脉向外生长形成的（Mikawa和Fischman，1992）。为了研究冠状平滑肌细胞的起源，用活性染料（DiI）或编码β-半乳糖苷酶的复制缺陷型逆转录病毒标记产生心包细胞的前心外膜器官。通过在卵内直接靶向前心外膜中假定的血管生成细胞，或在体外标记解剖的前心外膜细胞，然后移植到阶段匹配的宿主胚胎中，实现细胞谱系标记。在冠状血管生成过程中对标记细胞的监测表明，前心外膜来源的细胞并入了三个与血管相关的群体；冠状平滑肌、血管周围结缔组织和内皮细胞。免疫共聚焦显微镜在器官中识别出内皮细胞和平滑肌细胞群体。结果表明：（1）前心外膜含有冠状平滑肌细胞的祖细胞群体，其随着心包向内生长而迁移到心脏中；（2）在迁移之前，冠状平滑肌谱系已经建立。
