Visconti Richard P, Awgulewitsch Alexander
Richard P Visconti, Alexander Awgulewitsch, Department of Regenerative Medicine and Cell Biology, Medical University of South Carolina, Charleston, SC 29425, United States.
World J Biol Chem. 2015 Aug 26;6(3):65-70. doi: 10.4331/wjbc.v6.i3.65.
Steadily increasing evidence supports the idea that genetic diversities in the vascular bed are, in addition to hemodynamic influences, a major contributing factor in determining region-specific cardiovascular disease susceptibility. Members of the phylogenetically highly conserved Hox gene family of developmental regulators have to be viewed as prime candidates for determining these regional genetic differences in the vasculature. During embryonic patterning, the regionally distinct and precisely choreographed expression patterns of HOX transcription factors are essential for the correct specification of positional identities. Apparently, these topographic patterns are to some degree retained in certain adult tissues, including the circulatory system. While an understanding of the functional significance of these localized Hox activities in adult blood vessels is only beginning to emerge, an argument can be made for a role of Hox genes in the maintenance of vessel wall homeostasis and functional integrity on the one hand, and in regulating the development and progression of regionally restricted vascular pathologies, on the other. Initial functional studies in animal models, as well as data from clinical studies provide some level of support for this view. The data suggest that putative genetic regulatory networks of Hox-dependent cardiovascular disease processes include genes of diverse functional categories (extracellular matrix remodeling, transmembrane signaling, cell cycle control, inflammatory response, transcriptional control, etc.), as potential targets in both vascular smooth muscle and endothelial cells, as well as cell populations residing in the adventitia.
越来越多的证据支持这样一种观点，即除血流动力学影响外，血管床中的基因多样性是决定区域特异性心血管疾病易感性的主要因素。发育调节因子中系统发育高度保守的Hox基因家族成员必须被视为决定血管中这些区域基因差异的主要候选者。在胚胎模式形成过程中，HOX转录因子区域特异性且精确编排的表达模式对于正确确定位置身份至关重要。显然，这些地形模式在某些成年组织中，包括循环系统，在一定程度上得以保留。虽然对成年血管中这些局部Hox活性的功能意义的理解才刚刚开始，但一方面可以认为Hox基因在维持血管壁稳态和功能完整性方面发挥作用，另一方面在调节区域局限性血管病变的发展和进程中发挥作用。动物模型的初步功能研究以及临床研究数据为这一观点提供了一定程度的支持。数据表明，Hox依赖性心血管疾病过程的假定遗传调控网络包括不同功能类别的基因（细胞外基质重塑、跨膜信号传导、细胞周期控制、炎症反应、转录控制等），作为血管平滑肌和内皮细胞以及外膜中细胞群体的潜在靶点。
