Arterial smooth muscle.
Arterial smooth muscle.
复制标题
DOI：
10.1161/atvbaha.114.304441
复制
发表时间：
2014-10
期刊：
影响因子：
--
通讯作者：
Bornfeldt KE
中科院分区：
文献类型：
--
作者：
Wall VZ;Bornfeldt KE
SMCs也可以具有其他细胞类型的特性。例如，人们早就知道动脉粥样硬化病变中的SMCs能够积累胆固醇，因此类似于巨噬细胞泡沫细胞。根据平滑肌α-肌动蛋白的表达，人类冠状动脉病变中多达50%的油红o阳性泡沫细胞被鉴定为SMCs。最近，米色脂肪细胞也被确定为具有平滑肌样起源。此外，在导致血管钙化的过程中，SMCs在很大程度上失去了平滑肌α-肌动蛋白和平滑肌22α的表达，并通过一个至少部分依赖于钠依赖性磷酸盐共转运蛋白Pit-1和Pit-2的过程获得了骨形成蛋白的表达，这一过程通过冗余机制促进钙化13，并通过肿瘤坏死因子相关蛋白3,14，骨保护素，15和血管紧张素II起作用。使SMCs的身份进一步复杂化的是，SMCs在脉管系统中的起源是多种多样的，不同的动脉或动脉段含有不同发育起源的SMCs。17在小鼠中，在主动脉弓和主动脉弓分支的动脉中发现了神经嵴衍生的SMCs，例如在小鼠模型中经常用于研究动脉粥样硬化的头臂动脉。胸主动脉的间充质干细胞来源于小体，而腹主动脉的间充质干细胞主要来源于内脏中胚层。17此外，其他动脉中也存在其他谱系，干细胞和成血管细胞也有助于不同动脉中SMCs的组成。尽管上述表型转换似乎对所有SMCs都是共同的，无论其来源如何，但这些SMCs对各种刺激的反应不同。基于这些信息，最近的一项研究表明，SMCs的区域表型变异性有助于其对肿瘤坏死因子-α刺激的核因子-κB活性的调节。18,19这些有趣的发现可能解释了在全身性炎症升高的情况下，不同动脉的动脉粥样硬化易感性的差异。
SMCs can also take on properties of other cell types. For example, SMCs in atherosclerotic lesions have long been known to be able to accumulate cholesterol and thereby resemble macrophage foam cells. As much as 50% of oil red O–positive foam cells in human coronary artery lesions have been identified as SMCs, based on their expression of smooth muscle α-actin. 11 Recently, beige adipocytes have also been identified as having a smooth muscle–like origin. 12 Furthermore, during the process leading to vascular calcification, SMCs largely lose their expression of smooth muscle α-actin and smooth muscle 22α and gain expression of bone-forming proteins through a process, at least in part, dependent on the sodium-dependent phosphate cotransporters Pit-1 and Pit-2, which act through redundant mechanisms to promote calcification13 and through tumor necrosis factor–related protein-3, 14 osteoprotegerin, 15 and angiotensin II. 16To complicate the identity of SMCs further, the origin of SMCs in the vasculature is diverse, and different arteries or segments of arteries contain SMCs of different developmental origin. 17 In the mouse, neural crest-derived SMCs are found in the aortic arch and arteries branching off of the arch, such as the brachiocephalic artery often used for studies of atherosclerosis in mouse models. SMCs in the thoracic aorta are derived from somites, whereas SMCs in the abdominal aorta are derived primarily from splanchnic mesoderm. 17 In addition, other lineages exist in other arteries, and stem cells and mesangioblasts also contribute to the composition of SMCs in different arteries. Although the phenotypic switching described above seems to be common to all SMCs regardless of origin, these SMCs respond differently to various stimuli. 17 Building on this information, a recent study demonstrated that regional phenotypic variability of SMCs contributes to their regulation of nuclear factor-κB activity in response to tumor necrosis factor-α stimulation. 18, 19 These interesting findings might explain the differences in atherosclerosis susceptibility of different arteries under conditions in which systemic inflammation is elevated.