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发育过程中主动脉的研究。I. 离体和体外条件下的胎兔主动脉:器官培养时平滑肌细胞表型、细胞增殖及胆固醇含量的快速变化

Studies on aorta during development. I. Fetal rabbit aorta under ex vivo and in vitro conditions: rapid changes in smooth muscle cell phenotype, cell proliferation and cholesterol content with organ culture.

作者信息

Sprinkle D J, Subbiah M T

机构信息

Department of Internal Medicine, University of Cincinnati Medical Center, OH 45267.

出版信息

Atherosclerosis. 1987 Sep;67(1):57-69. doi: 10.1016/0021-9150(87)90265-6.

DOI:10.1016/0021-9150(87)90265-6
PMID:3675706
Abstract

The structural development of the already well defined fetal rabbit aortic wall from 22 to 31 days of gestation in vivo consists of increasing aortic wall thickness, elastic lamina continuities, extracellular matrix deposition, and maturing of the fine structure of the medial smooth muscle cells. In vivo at term (31 days), the mature aortic smooth muscle cells demonstrated the characteristic thin, thick and intermediate filaments, dense plaques, endoplasmic reticulum, golgi, plasmalemma vesicles and an incomplete basal lamina. The fetal aorta rapidly responded to organ culture with various changes. Fetal smooth muscle cells modified their phenotype to the synthetic state when cultured in both serum-supplemented and serum-free media. This smooth muscle cell modification occurred after 3 days of culture in fetal explants. The synthetic type smooth muscle cells (fetal) began to proliferate after 6 days of culture. This proliferation resulted in a peripheral outgrowth after 9 days of 10-20 layers in fetal cultures from serum-supplemented media and of 2-4 layers in serum-free media. The orderly arrangement of the internal elastic lamina and alternating medial layers of smooth muscle cells and elastic lamina seen in vivo was disrupted along with increased matrix after 9 days of fetal explant culture. Significant numbers of 'modified' synthetic phenotype smooth muscle cells were not observed in adult aortic explants until after 15 days in culture in serum supplemented media. The mature contractile phenotype smooth muscle cell predominated in adult explants cultured in serum-free media. Significant synthetic phenotype smooth muscle cell proliferation only occurred in adult explants after 15 days culture in serum-supplemented media. When compared to aorta in vivo evidence for increases in cholesterol esterification were observed in both fetal (9 days) and adult (15 days) explants cultured in both serum-supplemented and serum-free media. The fetal aorta in organ culture appeared to be more susceptible than the adult aorta to (a) phenotypic modulation of smooth muscle cells to the synthetic state, (b) smooth muscle cell proliferation, and (c) early cholesteryl ester accumulation.

摘要

妊娠22至31天的胎兔主动脉壁在体内已发育良好,其结构发育包括主动脉壁厚度增加、弹性膜连续性增强、细胞外基质沉积以及中膜平滑肌细胞精细结构的成熟。足月时(31天)在体内,成熟的主动脉平滑肌细胞表现出特征性的细肌丝、粗肌丝和中间丝、致密斑、内质网、高尔基体、质膜小泡以及不完整的基膜。胎主动脉对器官培养迅速产生各种变化。在添加血清和无血清培养基中培养时,胎儿平滑肌细胞将其表型转变为合成状态。这种平滑肌细胞的改变在胎儿外植体培养3天后发生。合成型平滑肌细胞(胎儿)在培养6天后开始增殖。这种增殖在培养9天后导致外周生长,在添加血清的培养基中胎儿培养物中形成10 - 20层,在无血清培养基中形成2 - 4层。胎儿外植体培养9天后,体内可见的内弹性膜的有序排列以及平滑肌细胞和弹性膜交替的中层结构被破坏,同时基质增加。在添加血清的培养基中培养15天后,在成年主动脉外植体中才观察到大量“修饰”的合成表型平滑肌细胞。在无血清培养基中培养的成年外植体中,成熟的收缩表型平滑肌细胞占主导。仅在添加血清的培养基中培养15天后,成年外植体中才发生显著的合成表型平滑肌细胞增殖。与体内主动脉相比,在添加血清和无血清培养基中培养的胎儿(9天)和成年(15天)外植体中均观察到胆固醇酯化增加的证据。器官培养中的胎儿主动脉似乎比成年主动脉更容易受到以下影响:(a)平滑肌细胞向合成状态的表型调节;(b)平滑肌细胞增殖;(c)早期胆固醇酯积累。

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