The role of oxygen transport in atherosclerosis and vascular disease

Abstract

<jats:p>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.</jats:p>

The deleterious effects of acute hypoxia on microvascular and large vessel endothelial function

“…Chronic and acute hypoxic exposure has been shown to trigger endothelial damage and vascular inflammation (Tarbell et al, 2020), increasing an individual's risk of vascular injury that can lead to adverse outcomes, such as cardiovascular disease (Lee et al, 2019). Moreover, the progressive nature of cardiovascular disease is also proposed to exacerbate vascular hypoxia (Gupta & Zahid Ashraf, 2018), resulting in a reciprocal cycle.…”

Characterization of Spontaneous Vascular Findings in the Papillary Muscles of Beagle Dogs

“…Furthermore, high incidence of intimal hyperplasia is also consistent with physiologic response to regional hypoxia and/or turbulent blood flow. [15][16][17] These changes could not have arisen postmortem. Masson's trichrome staining also demonstrated deposition of collagen within the medial tunic of many coronary vessels, also indicating a physiologic remodeling response.…”

Imaging Inflammation in Patients and Animals: Focus on PET Imaging the Vulnerable Plaque

“…Hypoxia has been reported in plaques from humans and animal models of atherosclerosis. In atherosclerosis and vascular disease of larger arteries, hypoxia occurs within layers of the arterial wall [66]. Hypoxia stimulates pro-atherosclerotic processes, including deficient lipid efflux, inflammation, interference with macrophage polarization, and glucose metabolism [67].…”

“…Hypoxia stimulates pro-atherosclerotic processes, including deficient lipid efflux, inflammation, interference with macrophage polarization, and glucose metabolism [67]. The exact mechanisms of hypoxia in atherosclerosis remain unclear, but may involve hypoxia-inducible factor (HIF)-1α and NF-κB, signalling pathways implicated in inflammation and hypoxia [66]. Both HIF-1α and NF-κB are activated by the same proinflammatory stimuli (TNF-α and IL-6), disturbed blood flow and oxidative stress [68,69].…”