Models of vascular injury and the potential therapeutic benefits of magnesium supplementation
Wallace, Robert G.
(2020)
Models of vascular injury and the potential therapeutic benefits of magnesium supplementation.
PhD thesis, Dublin City University.
Epigenetic modification, the accumulation of distinct chemical signatures on DNA and histones, are initially established during embryogenesis and continue to be modified by age and lifestyle choices throughout life. Expression of non-coding RNA, such as microRNA (miRNA), play a regulatory role in gene expression as well as epigenetic mechanisms. Blood vessels are readily capable of re-modelling their structures in response to hemodynamic prompts associated with variations in blood flow. Injurious oscillatory shear stress (OSS) associated with atherosclerosis, in particular, is believed to exert a damaging influence on the health and epigenetic processes of the vascular endothelium. Vascular inflammation is a key contributor to cardiovascular diseases (CVD), with inflammation and CVD risk factors closely inter- related. Atherosclerosis, the most common of the vascular inflammatory diseases, is defined as chronic, specifically affecting arterial blood vessels, and caused by dynamic dysfunction of endothelium. For the initial part of this work, we employed an endothelial cell model of OSS to investigate the relationship between miRNA expression and epigenetic mechanisms during an atherosclerotic challenge. Our results show that human aortic endothelial cells (HAECs) exhibit a clear epigenetic response to OSS in a time-dependent manner, most pronounced at 48 h.
Using our established OSS model, we next examined the anti-inflammatory response of the endothelium to a magnesium-based seawater extract in comparison to other forms of magnesium. Nutritional magnesium supplementation may act beneficially through epigenetic mechanisms, as well as traditional cellular and molecular pathways. In parallel with this, a human trial to assess the beneficial effects of a magnesium-based supplement mixture on vascular competence was conducted. Our results indicate that magnesium elicits beneficial effects on platelets and the vascular compartment through reduced platelet adhesion and aggregation.
We finally investigated the anti-inflammatory effects of magnesium supplementation on an in vitro dermal burn model, which included examining the ability of magnesium
to improve the angiogenic and migratory potential of endothelial cells, an essential feature of the wound healing process. Our results indicate that magnesium constitutes an important molecular constituent in this process, leading to amplified expression of a number of wound healing mechanisms and increasing response at a cellular level. As such, the inclusion of magnesium as a therapeutic aid in the stabilisation of burn injuries is a warranted addition.