​Endothelial Cell Biology Theme

Background

Vascular endothelial cells (ECs) are dynamic and play a key role in maintaining cardiovascular homeostasis. In addition to serving as a physical barrier between the vessel wall and lumen, ECs are metabolically active, and produce mediators that affect vascular tone, cell adhesion, the homeostasis of clotting, and fibrinolysis3. They exert autocrine, paracrine and endocrine actions and regulate platelet aggregation, coagulation, fibrinolysis, and cardiovascular homeostasis2, 3.

Exposure of vascular ECs to pathophysiological conditions, such as hyperglycemia, hypercholesterolemia, hypertension, and stress etc., causes EC dysfunction and activation. It is commonly agreed that EC dysfunction and activation play key roles in atherosclerosis, coronary artery disease, diabetes, hypertension, and normal physiological ageing. Endothelial dysfunction is considered an early marker for atherosclerosis. It is an important event in the development of microvascular complications in diabetes.

The endothelial cell theme is focusing on 1. using ECs regenerated from progeria patient derived hiPSCs (PG-hiPSCs) as disease EC models for studying endothelial dysfunction and 2. Determining the disease-specific phenotypes and underlying genomic mechanisms of primary ECs derived from human saphenous vein or internal mammary artery from patients with coronary artery disease (CAD). These have major implications for developing a promising platform to use human ECs for screening high-throughput drugs, identifying genes involving atherosclerosis, and assessing potential novel gene or cell therapies for treatment of CAD.

Protein expression of CD31 (A), CD144 (B), and vWF-8 (C) from endothelial cells  (ECs) differentiated from human induced pluripotent stem cells (hiPSCs) were evaluated via immunofluorescence; nuclei were counterstained with DAPI. The biological function of hiPSC-ECs was evaluated by tube-like structure formation on Matrigel (D).

Research Area

1. Progeria patient derived hiPSCs (PG-hiPSCs) regenerated ECs (PG-hiPSCs-ECs) as disease EC models in vitro
2. Identifying critical determinants of endothelial cell biology using integrated genomic and phenotyping approaches in primary ECs
3. Deciphering the underlying mechanism of 3D fibrin scaffolds for efficient EC differentiation from hiPSCs

Achievements​

Grants

1. NMRC Clinician Scientist Individual Research Grant (PI: Dr Ye Lei): “Synergy between Thymosin B4 and Cardiomyocytes for Cardiac protection, regeneration and metabolism”
2. Singhealth Foundation Research grant (PI: Dr. Ye Lei): "The role and mechanism of titin truncation variation following myocardial injury"
3. NMRC Open-Fund Individual Research Grant (PI: Dr Ye Lei): "Myocardial regeneration of neonatal pig"