Endothelial cell metabolism in health and disease: impact of hypoxia

Abstract

In contrast to the general belief, endothelial cell (EC) metabolism has recently been identified as a driver rather than a bystander effect of angiogenesis in health and disease. Indeed, different EC subtypes present with distinct metabolic properties, which determine their function in angiogenesis upon growth factor stimulation. One of the main stimulators of angiogenesis is hypoxia, frequently observed in disease settings such as cancer and atherosclerosis. It has long been established that hypoxic signalling and metabolism changes are highly interlinked. In this review, we will provide an overview of the literature and recent findings on hypoxia-driven EC function and metabolism in health and disease. We summarize evidence on metabolic crosstalk between different hypoxic cell types with ECs and suggest new metabolic targets.

Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout

“…Furthermore, hypoxia or oxygen deficiency is a prominent feature of solid tumours. Hypoxic tumours are often resistant to conventional cancer therapies, and tumour hypoxia correlates with advanced stages of malignancy and metastasis . We further investigated the potential lncRNAs regulated by hypoxia.…”

Endothelial cells and organ function: applications and implications of understanding unique and reciprocal remodelling

“…Oxygen sensing is essential for homeostasis and management of cellular energy, and one of the most important roles of the vasculature. It has been extensively described in the lung endothelium , which distinctly responds with vasoconstriction to drops in atmospheric oxygen, instead of the vasodilation observed in every other capillary network; The effect of O 2 availability has also been thoroughly studied in tumours, where the environment is hypoxic, perfusion is deficient, and angiogenic factors are abundant . The sensing and response to atmospheric oxygen levels are vital to mammalian energetic strategy, and the skin is a known key peripheral sensor that can alone modulate systemic blood flow .…”

“…Other microvascular properties that are unique to certain microenvironments include angiogenic potential , angiocrine/endocrine profile and metabolic rates ; all are essential functional parameters, and all are tissue‐specific.…”

“…A large body of work has been dedicated to EC in very unique pathologies, such as in the tumour vasculature and diabetic retinopathy , which have provided valuable breakthroughs in vascular biology and metabolism. Yet, this knowledge is limited in the representation of the impact of EC dysfunction as both cause and effect of other conditions, including lifestyle and ageing, which can neither be generalized and applied to all EC populations, nor seamlessly translated between model organisms.…”

Oxidized low‐density lipoprotein promotes vascular endothelial cell dysfunction by stimulating miR‐496 expression and inhibiting the Hippo pathway effector YAP

“…During atherosclerosis progression, macrophages participate in the local inflammatory responses by secreting cytokines, free radicals, proteases, and various supplements, and mediate low-density lipoprotein (LDL) oxidation by producing reactive oxygen species and reactive nitrogen species, and forming oxidized LDL (ox-LDL) (Bories and Leitinger, 2017;Wong et al, 2017;Xiao et al, 2017). During atherosclerosis progression, macrophages participate in the local inflammatory responses by secreting cytokines, free radicals, proteases, and various supplements, and mediate low-density lipoprotein (LDL) oxidation by producing reactive oxygen species and reactive nitrogen species, and forming oxidized LDL (ox-LDL) (Bories and Leitinger, 2017;Wong et al, 2017;Xiao et al, 2017).…”