EP_075. The effect of navitoclax on hypoxia-induced human endothelial cell in vitro angiogenesis model

Nur Najmi Mohamad Anuar^1,5*, Cheang Kah Wai¹, Maisarah Md Razmi¹,  Azizah Ugusman^2,5, Nadiah Sulaiman^3,5, Mohd Faizal Ahmad⁴

1. Programme of Biomedical Science, Centre for Toxicology & Health Risk Studies, Faculty of Health Sciences, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, 50300 Kuala Lumpur, Malaysia

2. Department of Physiology, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia

3. Department of Tissue Engineering & Regenerative Medicine, Faculty of Medicine, Universiti Kebangsaan Malaysia, 56000 Kuala Lumpur, Malaysia

4. Department of Obstetrics & Gynaecology, Tunku Mukhriz Chancellor Hospital, Universiti Kebangsaan Malaysia Medical Centre, Jalan Yaacob Latif, Bandar Tun Razak, Cheras, 56000 Kuala Lumpur, Malaysia

5. Cardiovascular and Pulmonary Research Group (CardioResp), Universiti Kebangsaan Malaysia, 43600 Bangi, Malaysia

*Corresponding author: Nur Najmi Mohamad Anuar. This email address is being protected from spambots. You need JavaScript enabled to view it.

ABSTRACT

INTRODUCTION:  Hypoxia is defined as the reduction of oxygen tension below its normal range within a particular tissue. Under hypoxia, numerous angiogenic pathways will stimulate new blood vessel formation to ensure sufficient oxygen supply. However, intraplaque neovascularisation within atherosclerosis can contribute to plaque instability. Several anti-angiogenic drugs, such as anti-VEGF drugs have demonstrated side effects that may limit their usage. Navitoclax was found to induce cell apoptosis in cancer cells; hence, it is suggested to be a potential new therapeutic strategy for plaque instability in atherosclerosis by reducing endothelial cell survival.

OBJECTIVE(S): This study aimed to investigate the role of navitoclax in a hypoxia-induced human endothelial cell angiogenesis model.

MATERIALS & METHODS: Cell viability was determined through a cell viability assay (MTT) and angiogenesis activity via angiogenesis assay under normoxic conditions (control) (21% oxygen, 5% carbon dioxide, and 64% nitrogen) and hypoxic conditions (1% oxygen, 5% carbon dioxide, and 94% nitrogen). Lastly, the effect of hypoxic conditions treated with navitoclax, 0.5 μM, was identified through an angiogenesis assay.

RESULTS: The result of this study showed a reduction of tube formation in the hypoxia+navitoclax group. The total tube length, the number of meshes, junctions, and segments were significantly (p < 0.0001) lower than the hypoxia group after incubation at 2, 4, and 6 hours.

CONCLUSION: Hence, navitoclax exhibits anti-angiogenesis effects by reducing the tube formation in hypoxia-induced angiogenesis in HUVEC, indicating that it has the potential to act as an anti-angiogenic drug under hypoxic conditions.

KEYWORDS: Atherosclerosis, Angiogenesis, HUVEC, Hypoxia, Navitoclax