Retinoids: versatile biological response modifiers of vascular smooth muscle phenotype.
Retinoids: versatile biological response modifiers of vascular smooth muscle phenotype.
复制标题
类维生素A：血管平滑肌表型的多功能生物反应调节剂。
DOI：
10.1161/01.res.87.5.355
复制
发表时间：
2000
影响因子：
20.1
通讯作者：
Berk,BC
中科院分区：
文献类型：
--
作者：
Miano,JM;Berk,BC
血管平滑肌细胞（SMC）分化和生长的适当调节对于血管生成和成熟血管壁稳态的维持至关重要。 1, 2 控制 SMC 分化和生长的分子回路的扰动被认为对于动脉粥样硬化、高血压和血运重建后再狭窄的发病机制至关重要。膜结合受体的鉴定及其各自信号通路的描绘使我们深入了解了控制 SMC 分化和生长的机制，并为血管疾病的治疗提供了分子靶点。 4 近年来，多种核受体结合因子已被证明可以调节 SMC 的分化和生长。类固醇受体超家族5在这方面特别受关注。类固醇受体是配体激活的转录因子，可在越来越多的靶基因的调控区域内结合离散的顺式元件。该核受体家族包括雌激素受体、6 维生素 D 受体、7 过氧化物酶体增殖物激活受体、8 和类视黄醇受体。 9 类视黄醇及其结合的受体在心血管发育和血管对损伤的反应中发挥着越来越重要的作用。在这篇综述中，我们将特别关注类维生素A作为血管平滑肌细胞分化和生长的关键调节剂的新兴作用。我们首先提供类视黄醇生物学的简史及其细胞内命运，特别强调类视黄醇受体。然后，我们总结了迄今为止支持类视黄醇作为血管生成和 SMC 分化调节剂的文献。然后考虑类视黄醇在控制 SMC 生长中的作用的最新情况，然后总结最近显示类视黄醇给药抑制新内膜形成的证实论文。我们对未来的研究进行了总结，未来应该进行研究，以深入了解这些多效性生物反应调节剂如何调节血管 SMC 表型。
Proper regulation of vascular smooth muscle cell (SMC) differentiation and growth is critical for vasculogenesis and the maintenance of homeostasis in the mature vessel wall. 1, 2 Perturbations in the molecular circuitry governing SMC differentiation and growth are thought to be of central importance in the pathogenesis of atherosclerosis, hypertension, and restenosis after procedural revascularizations. The identification of membrane-bound receptors and the delineation of their respective signaling pathways have yielded insight into the mechanisms that control SMC differentiation and growth3 and have provided molecular targets for therapy of vascular disease. 4 In recent years, several nuclear receptor binding factors have been shown to regulate SMC differentiation and growth. The steroid receptor superfamily5 has been of particular interest in this regard. Steroid receptors are ligand-activated transcription factors that bind discrete cis elements within the regulatory regions of a growing list of target genes. This family of nuclear receptors includes the estrogen receptors, 6 the vitamin D receptor, 7 the peroxisome proliferator-activated receptors, 8 and the retinoid receptors. 9 Retinoids and the receptors they bind are gaining an increasingly important role in both cardiovascular development and the response of blood vessels to injury. In this review, we will focus specifically on the emerging role of retinoids as critical regulators of vascular SMC differentiation and growth. We first provide a brief history of retinoid biology as well as its intracellular fates with particular emphasis on the retinoid receptors. We then summarize the literature to date supporting retinoids as regulators of vasculogenesis and SMC differentiation. An update on the role of retinoids in the control of SMC growth is then considered followed by a summary of the recent corroborative papers showing an inhibition of neointimal formation with retinoid administration. We conclude the review with future studies that should be pursued to gain mechanistic insight into how these pleiotropic biological response modifiers regulate vascular SMC phenotype.