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.

Single‐cell transcriptional profiling of human carotid plaques reveals a subpopulation of endothelial cells associated with stroke incidences

“…EC subpopulations with different phenotypes including proliferative ECs, inflammatory ECs, remodelling ECs, ECs involved in endothelial‐mesenchymal transition (EndMT) and ECs involved in angiogenesis were identified under different stimuli such as oxidative stress, vascular injury and disturbed flow. 19 Importantly, EC subpopulation involved in angiogenesis was reported in normal mouse aortic cells using single‐cell RNA‐sequencing, 11 which is consistent with the top 1 biological process of EC 1 we detected. EC 3 subpopulation was more specialized in the proliferation of smooth muscle cells and osteoblast differentiation possibly in line with mesenchymal‐like cells that undergo a phenotypic switch towards a mesenchymal phenotype.…”

Proper Rac1 Required for Ang2 - AT2 Activities for Cardiomyocytes and ECs Where Tyr TAT and TAC Kinases Required for Preventing Glycoprotein Storage and Glycogen Accumulation

“…Endothelial cells have been shown to have an important role in calcific aortic valve disease. As observed in atherosclerosis, ECs exposed to mechanical or shear stress become dysfunctional, with increased lipid deposition and immune cell infiltration, that Alteration of EC gene expression is an early event in vascular disease and plays a critical role in its progression [67]. So, inhibition in proper Rac1 synthesis due to inhibition in Proline, in Tyr, and other necessary hydrophobic amino acids will lead to alterations in Rac1 Molecular structures and activities that will affect in the alterations of ECs gene expression and will lead to vascular diseases.…”

Integrative single-cell meta-analysis reveals disease-relevant vascular cell states and markers in human atherosclerosis

“…Next, we surveyed the 41 clusters using a combination of automated and manual annotation (Methods). Manual annotations included markers of lymphoid, myeloid and endothelial cell subtypes from the literature [21][22][23][44][45][46][47][48][49] . We then verified manual annotations using the CellTypist machine learning classifier 50 resulting in a more granular map of cell diversity in human atherosclerosis (Fig.…”

“…Gene markers for level 1 annotations were obtained using the PrepSCTMarkers() and FindAllMarkers() functions from Seurat (v.4.1.0) setting the following thresholds: logFC=0.25 and min.pct=0.25 Level 2 annotations for endothelial, fibroblasts and immune cells: To define more granular cell subtypes for the meta-analyzed data, we used a combination of automated and manual annotations. We first annotated cell subtypes for endothelial, myeloid and lymphoid lineages using markers from atherosclerosis murine scRNA meta-analyses of SMCs and immune cells as well as relevant human atherosclerosis scRNA studies [21][22][23][44][45][46][47][48][49] . Annotations using curated markers from the literature were corroborated with the assistance of experts at UVA.…”