Date of Completion

12-2-2019

Embargo Period

12-2-2029

Keywords

Atherosclerosis, Bioactives, Nutrition, Heart Disease, Microbiota

Major Advisor

Dr. Christopher Blesso

Associate Advisor

Dr. Ji-Young Lee

Associate Advisor

Dr. Maria-Luz Fernandez

Associate Advisor

Dr. Young-Ki Park

Associate Advisor

Dr. José Manautou

Field of Study

Nutritional Science

Degree

Doctor of Philosophy

Open Access

Open Access

Abstract

Cardiovascular disease (CVD) is the leading cause of non-communicable disease in the United States. Atherosclerosis, the build-up of plaque within the intima of the artery, is a key contributor to CVD and a multi-factorial disorder of impaired lipid metabolism and inflammation. A plethora of pharmaceuticals have been developed in attempts to treat CVD; however, some are still left with residual risk despite use of medications. Diet is an attractive candidate to compliment current drug therapies for CVD, since the disease is multi-factorial. Some foods contain dietary bioactive compounds (DBCs) that are thought to have benefits beyond basic nutritional value. Not only do foods possess DBCs, but microbes residing in the gut flora also produce bioactive compounds that may be influenced by diet. Thus, this dissertation aimed to identify plant-, animal-, and microbe-derived bioactive compounds that may influence atherosclerosis development. In Aim 1, we investigated the effects of long-term supplementation with black elderberry extract (BEE) to apolipoprotein E knockout (apoE-/-) mice on a chow diet. We found that BEE improved markers of HDL function and plaque stability in the aortic root. However, no effect was seen on atherosclerotic lesion size. Aim 2 focused on the effects of egg sphingomyelin (ESM) supplementation to apoE-/- on a high-fat, added cholesterol diet. ESM supplementation had no effect on serum lipids; however, there was a significant reduction in both circulatory serum amyloid A (SAA) and total aortic root lesion size analyzed by Oil Red O. Aim 3 evaluated the effects of chronic, low-dose injection of a bacterial-derived serine dipeptide lipid, Lipid 654 (L-654). Contrary to our hypothesis, L-654 injected mice had significant reductions in serum lipids, hepatic injury, and aortic root total lesion area. Overall, this work demonstrates the potential for both dietary and microbial bioactives to influence CVD-related risk factors.

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Available for download on Sunday, December 02, 2029

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