Human semilunar cardiac valve remodeling by activated cells from fetus to adult - Implications for postnatal adaptation, pathology, and tissue engineering
Human semilunar cardiac valve remodeling by activated cells from fetus to adult - Implications for postnatal adaptation, pathology, and tissue engineering
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DOI：
10.1161/circulationaha.105.591768
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发表时间：
2006-03-14
期刊：
影响因子：
37.8
通讯作者：
Schoen, FJ
中科院分区：
文献类型：
--
作者：
Aikawa, E;Whittaker, P;Schoen, FJ
背景 - 心脏瓣膜在胎儿成熟期间以及通过衰老进行出生后适应过程中细胞表型和基质结构的演变仍未得到探索。
方法和结果 - 我们假设对维持瓣膜功能至关重要的瓣膜间质细胞（VIC）和内皮细胞（VEC）表型会在一生中因环境刺激而发生变化。我们对从妊娠14 - 19周和20 - 39周的胎儿、出生几分钟到30天的新生儿、2 - 16岁的儿童以及成年人获取的91个人类半月瓣进行了定量组织学评估。在妊娠36周时出现了三层结构，但与成人瓣膜相比仍很原始。在整个胎儿发育过程中，内皮细胞表达一种活化表型。胎儿瓣膜中的间质细胞密度、增殖和凋亡明显高于成人瓣膜。胎儿的肺动脉和主动脉间质细胞呈现出一种活化的肌成纤维细胞样表型（α - 肌动蛋白表达）、丰富的胚胎肌球蛋白以及基质金属蛋白酶 - 胶原酶，这表明其具有一种参与基质重塑的未成熟/活化表型，而成人则是一种静止的成纤维细胞样表型。出生时，从胎儿循环到新生儿循环的突然变化与新生儿主动脉瓣相比肺动脉瓣中更多的α - 肌动蛋白阳性间质细胞有关。胶原蛋白含量从胎儿早期到晚期增加，但随后保持不变，而弹性蛋白在出生后显著增加。胶原纤维颜色分析显示，细纤维逐渐减少，粗纤维相应增加。此外，成人瓣膜中的胶原纤维比胎儿瓣膜中的排列更整齐。
结论 - 胎儿瓣膜具有动态/适应性结构，并且包含具有活化/未成熟表型的细胞。在出生后的生命过程中，活化的细胞逐渐变得静止，而胶原蛋白逐渐成熟，这表明是一种渐进的、由环境介导的适应过程。
Background - The evolution of cell phenotypes and matrix architecture in cardiac valves during fetal maturation and postnatal adaptation through senescence remains unexplored.Methods and Results - We hypothesized that valvular interstitial (VIC) and endothelial cell (VEC) phenotypes, critical for maintaining valve function, change throughout life in response to environmental stimuli. We performed quantitative histological assessment of 91 human semilunar valves obtained from fetuses at 14 to 19 and 20 to 39 weeks' gestation; neonates minutes to 30 days old; children aged 2 to 16 years; and adults. A trilaminar architecture appeared by 36 weeks of gestation but remained rudimentary compared with that of adult valves. VECs expressed an activated phenotype throughout fetal development. VIC density, proliferation, and apoptosis were significantly higher in fetal than adult valves. Pulmonary and aortic fetal VICs showed an activated myofibroblast-like phenotype (alpha-actin expression), abundant embryonic myosin, and matrix metalloproteinase-collagenases, which indicates an immature/activated phenotype engaged in matrix remodeling versus a quiescent fibroblast-like phenotype in adults. At birth, the abrupt change from fetal to neonatal circulation was associated with a greater number of alpha-actin-positive VICs in neonatal aortic versus pulmonary valves. Collagen content increased from early to late fetal stages but was subsequently unchanged, whereas elastin significantly increased postnatally. Collagen fiber color analysis revealed a progressive temporal decrease in thin fibers and a corresponding increase in thick fibers. Additionally, collagen fibers were more aligned in adult than fetal valves.Conclusions - Fetal valves possess a dynamic/adaptive structure and contain cells with an activated/immature phenotype. During postnatal life, activated cells gradually become quiescent, whereas collagen matures, which suggests a progressive, environmentally mediated adaptation.