Electronic Thesis and Dissertation Repository

Thesis Format

Monograph

Degree

Master of Science

Program

Physiology and Pharmacology

Supervisor

Borradaile, Nica M.

Abstract

Observational studies have suggested an association between low levels of niacin and vitamin D and increased cardiovascular disease risk. Both vitamins have been shown to improve endothelial functions and vascular regeneration following vascular injury, however, it appears vitamin D may promote or inhibit neovascularization in a context-dependent manner. We hypothesized that supplementation of vitamin D alone and in combination with niacin, would improve endothelial cell function under lipotoxic conditions and promote revascularization and functional recovery in obese mice with ischemic injury. Matrigel assays, mRNA microarray analyses and growth rate assays were used to investigate angiogenic function of endothelial cells exposed to the saturated fatty acid, palmitate. Supplementation with vitamin D, niacin, and the combination improved endothelial tube formation and stability in high palmitate. Supplementation with vitamin D markedly decreased expression of cell cycle regulators, where niacin induced stable expression of miR126, a known regulator of angiogenesis. In diet-induced obese mice with acute ischemic injury, treatment with niacin, but not vitamin D or the combination, improved hind limb functional recovery. No significant improvements in revascularization, regeneration, inflammation, or fibrosis were observed. In conclusion, although both vitamins promoted in vitro endothelial cell angiogenic function, only niacin improved functional recovery following ischemic injury.

Summary for Lay Audience

In Canada, obesity, diabetes and metabolic syndrome are on the rise, especially among Canada’s Indigenous population. These diseases often lead to damaged blood vessels and cardiovascular diseases such as heart attack, stroke, hypertension, atherosclerosis and loss of blood flow to the lower legs, which can lead to amputation. These complications occur during obesity and diabetes due to the high levels of fats and sugars in the blood stream that damage endothelial cells, which make up the inner lining of blood vessels and maintain vessel function. One of the biggest challenges to our health care system is finding effective treatment options for patients with vascular disease. Both niacin (vitamin B3) and vitamin D have potential as alternative or complementary treatment options for vascular disease as they have been show to improve and maintain the function of endothelial cells. This project investigated whether vitamin D alone or in combination with niacin, could improve the ability of blood vessels to repair and regrow following damage caused by high fats. Supplementation with vitamin D, niacin, and the combination improved the ability of endothelial cells to form blood vessels in an experimental dish. However, in obese mice with hind leg blood vessel injury, supplementation with niacin alone, but not vitamin D or the combination, improved functional recovery of the hind leg. It is possible that vitamin D may limit the growth of new blood vessels during obesity as it was also found that vitamin D decreased the growth and expansion of endothelial cells when exposed to high fat. These findings raise questions as to effectiveness of vitamin D supplementation to promote cardiovascular health in a high fat setting such as obesity or metabolic syndrome. Ultimately, better understanding of the effects of nutritional compounds on blood vessels will help guide therapeutic and dietary recommendations for the promotion of vascular health.

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