Tarbell John, Mahmoud Marwa, Corti Andrea, Cardoso Luis, Caro Colin
Biomedical Engineering Department, The City College of New York, New York, NY, USA.
Department of Bioengineering, Imperial College London, London, UK.
J R Soc Interface. 2020 Apr;17(165):20190732. doi: 10.1098/rsif.2019.0732. Epub 2020 Apr 1.
Atherosclerosis and vascular disease of larger arteries are often associated with hypoxia within the layers of the vascular wall. In this review, we begin with a brief overview of the molecular changes in vascular cells associated with hypoxia and then emphasize the transport mechanisms that bring oxygen to cells within the vascular wall. We focus on fluid mechanical factors that control oxygen transport from lumenal blood flow to the intima and inner media layers of the artery, and solid mechanical factors that influence oxygen transport to the adventitia and outer media via the wall's microvascular system-the vasa vasorum (VV). Many cardiovascular risk factors are associated with VV compression that reduces VV perfusion and oxygenation. Dysfunctional VV neovascularization in response to hypoxia contributes to plaque inflammation and growth. Disturbed blood flow in vascular bifurcations and curvatures leads to reduced oxygen transport from blood to the inner layers of the wall and contributes to the development of atherosclerotic plaques in these regions. Recent studies have shown that hypoxia-inducible factor-1α (HIF-1α), a critical transcription factor associated with hypoxia, is also activated in disturbed flow by a mechanism that is independent of hypoxia. A final section of the review emphasizes hypoxia in vascular stenting that is used to enlarge vessels occluded by plaques. Stenting can compress the VV leading to hypoxia and associated intimal hyperplasia. To enhance oxygen transport during stenting, new stent designs with helical centrelines have been developed to increase blood phase oxygen transport rates and reduce intimal hyperplasia. Further study of the mechanisms controlling hypoxia in the artery wall may contribute to the development of therapeutic strategies for vascular diseases.
大动脉的动脉粥样硬化和血管疾病通常与血管壁各层内的缺氧有关。在本综述中，我们首先简要概述与缺氧相关的血管细胞分子变化，然后重点介绍将氧气输送到血管壁细胞的转运机制。我们关注控制氧气从管腔血流输送到动脉内膜和中膜内层的流体力学因素，以及通过血管壁的微血管系统——营养血管（VV）影响氧气输送到外膜和外中膜的固体力学因素。许多心血管危险因素与VV受压有关，这会降低VV灌注和氧合。缺氧时功能失调的VV新生血管形成会导致斑块炎症和生长。血管分叉和弯曲处的血流紊乱会导致从血液到血管壁内层的氧气输送减少，并促使这些区域动脉粥样硬化斑块的形成。最近的研究表明，缺氧诱导因子-1α（HIF-1α）是一种与缺氧相关的关键转录因子，在紊乱血流中也会通过一种独立于缺氧的机制被激活。综述的最后一部分强调了血管支架置入术中的缺氧情况，血管支架置入术用于扩大被斑块阻塞的血管。支架置入可压迫VV导致缺氧及相关的内膜增生。为了在支架置入过程中增强氧气输送，已开发出具有螺旋中心线的新型支架设计，以提高血相氧气输送速率并减少内膜增生。对控制动脉壁缺氧机制的进一步研究可能有助于开发血管疾病的治疗策略。
