Gifre-Renom Laia, Jones Elizabeth A V
Department of Cardiovascular Sciences, Centre for Molecular and Vascular Biology, KU Leuven, Leuven, Belgium.
Department of Cardiology, CARIM School for Cardiovascular Diseases, Maastricht University, Maastricht, Netherlands.
Front Physiol. 2021 Feb 25;12:639645. doi: 10.3389/fphys.2021.639645. eCollection 2021.
From developmental stages until adulthood, the circulatory system remodels in response to changes in blood flow in order to maintain vascular homeostasis. Remodeling processes can be driven by formation of vessels or angiogenesis, and by the restructuration of already existing vessels, such as vessel enlargement and regression. Notably, vessel enlargement can occur as fast as in few hours in response to changes in flow and pressure. The high plasticity and responsiveness of blood vessels rely on endothelial cells. Changes within the bloodstream, such as increasing shear stress in a narrowing vessel or lowering blood flow in redundant vessels, are sensed by endothelial cells and activate downstream signaling cascades, promoting behavioral changes in the involved cells. This way, endothelial cells can reorganize themselves to restore normal circulation levels within the vessel. However, the dysregulation of such processes can entail severe pathological circumstances with disturbances affecting diverse organs, such as human hereditary telangiectasias. There are different pathways through which endothelial cells react to promote vessel enlargement and mechanisms may differ depending on whether remodeling occurs in the adult or in developmental models. Understanding the molecular mechanisms involved in the fast-adapting processes governing vessel enlargement can open the door to a new set of therapeutical approaches to be applied in occlusive vascular diseases. Therefore, we have outlined here the latest advances in the study of vessel enlargement in physiology and pathology, with a special insight in the pathways involved in its regulation.
从发育阶段到成年期,循环系统会根据血流变化进行重塑,以维持血管稳态。重塑过程可由血管形成或血管生成驱动,也可由现有血管的重构驱动,如血管扩张和消退。值得注意的是,血管扩张可在数小时内迅速发生,以响应血流和压力的变化。血管的高可塑性和反应性依赖于内皮细胞。血流中的变化,如狭窄血管中剪切应力的增加或冗余血管中血流的降低,可被内皮细胞感知并激活下游信号级联反应,促进相关细胞的行为变化。通过这种方式,内皮细胞可以重新组织自身,以恢复血管内的正常循环水平。然而,这些过程的失调可能导致严重的病理情况,干扰影响多个器官,如人类遗传性毛细血管扩张症。内皮细胞通过不同途径对促进血管扩张做出反应,其机制可能因重塑发生在成人模型还是发育模型中而有所不同。了解快速适应血管扩张过程中涉及的分子机制,可为应用于闭塞性血管疾病的一系列新治疗方法打开大门。因此,我们在此概述了血管扩张在生理学和病理学研究中的最新进展,并特别深入探讨了其调节所涉及的途径。