Abstract
The vascular endothelium is characterized by a remarkable level of plasticity, which is the driving force not only of physiological repair/remodeling of adult tissues but also of pathological angiogenesis. The resulting heterogeneity of endothelial cells (ECs) makes targeting the endothelium challenging, no less because many EC phenotypes are yet to be identified and functionally inventorized. Efforts to map the vasculature at the single-cell level have been instrumental to capture the diversity of EC types and states at a remarkable depth in both normal and pathological states. Here, we discuss new EC subtypes and functions emerging from recent single-cell studies in health and disease. Interestingly, such studies revealed distinct metabolic gene signatures in different EC phenotypes, which deserve further consideration for therapy. We highlight how this metabolic targeting strategy could potentially be used to promote (for tissue repair) or block (in tumor) angiogenesis in a tissue or even vascular bed-specific manner.
Highlights
The vascular endothelium is heterogeneous as it dynamically engages in different functions, influenced by the physiological needs, energetic demands, and distinct conditions of different tissues
While we recognize that mural and smooth muscle cells are important players of the vasculature, we mainly focus here on endothelial cells (ECs) heterogeneity and highlight key examples of EC plasticity, including (i) the diversification/specification of the vascular endothelium in distinct subtypes and (ii) EC plasticity
We discuss how the vascular endothelium is endowed with different functions that are carried out by specialized EC subtypes, capable of switching phenotypes partially through reprogramming their metabolism
Summary
The vascular endothelium is heterogeneous as it dynamically engages in different functions, influenced by the physiological needs, energetic demands, and distinct conditions of different tissues.
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