New Technologies With Increased Precision Improve Understanding of Endothelial Cell Heterogeneity in Cardiovascular Health and Disease

Abstract

Endothelial cells (ECs) are vital for blood vessel integrity and have roles in maintaining normal vascular function, healing after injury, and vascular dysfunction. Extensive phenotypic heterogeneity has been observed among ECs of different types of blood vessels in the normal and diseased vascular wall. Although ECs with different phenotypes can share common functions, each has unique features that may dictate a fine-tuned role in vascular health and disease. Recent studies performed with single-cell technology have generated powerful information that has significantly improved our understanding of EC biology. Here, we summarize a variety of EC types, states, and phenotypes recently identified by using new, increasingly precise techniques in transcriptome analysis.

Keywords: atherosclerosis; cardiac disease; endothelial cell heterogeneity; endothelial mesenchymal transition; transcriptomics; vascular disease; vascular remodeling and arteriogenesis.

FIGURE 1

Endothelial cell heterogeneity revealed by cell-specific sequencing. Endothelial cells (ECs) exhibit phenotypic differences that stem from inherent organo-specific, vessel-specific, and site-specific functions. Additionally, ECs can change phenotypes in response to cell stress or vascular disease, with representative pathways and transcription factors promoting different phenotypes, as shown with the associated arrows. The isolation and sequencing of single cells allow for improved precision in determining different endothelial cell phenotypes or cell states. Although distinct phenotypes have been identified, some features overlap, such as proliferative stalk cells in vasculogenesis. Evidence supports a potential phenotypic spectrum of some types of ECs, such as those involved in remodeling and endothelial-mesenchymal transition.