2017 Cardiovascular Research Day Abstract Book

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Dietary Effects on Lipoprotein-Associated Bioactive Mediators of Atherosclerosis
Cody Sutphin 1 • Maria Kraemer, PhD 2 • Pan Deng, PhD 2 • Courtney Hammill, PhD 2 •
Susan Smyth, MD, PhD 2 • Andrew Morris, PhD 2
1Eastern Kentucky University • 2 Cardiovascular Research Center, University of Kentucky
Undergraduate
Elevated circulating levels of atherogenic lipoproteins associate with increased risk of
cardiovascular disease. Multiple lines of evidence implicate bioactive components of lipoprotein
particles (such as oxidized phospholipids) as signaling molecules that provoke responses in blood
and vascular cells that cause the development and progression of atherosclerosis. Studies from
ourselves and others identify a role for the bioactive lipid mediator lysophosphatidic acid (LPA) as
a proinflammatory atherogenic signal in preclinical models and clinical settings. LPA accumulates
in atheromas, and mice lacking certain LPA receptors are protected from experimentally induced
atherosclerosis while mice lacking the LPA degrading enzyme lipid phosphate phosphatase 3
(LPP3) exhibit accelerated atherosclerosis. These findings may explain why coronary artery disease
risk is elevated in individuals with common genetic polymorphisms that decrease LPP3 expression.
We hypothesized that LPA associated with low-density lipoprotein particles is sensitive to diet and
enhanced by genetic hyperlipidemia. Plasma LDL-associated lipid species were analyzed in WT and
LDLr-/- mice that were on either control or western diet. Mouse plasma was fractionated by sizeexclusion
chromatography using a calibrated Superose 6 column to separate lipoprotein species
and then analyzed by targeted and untargeted HPLC coupled mass spectrometry to identify and
quantitate LPA species, as well as other lipid-class species, that were altered in LDL-containing
plasma fractions. We found that circulating levels of LPA are highly sensitive to high fat feeding in
mice and that genetic manipulations that reduce lipoprotein clearance (Ldlr-/-) dramatically
increase circulating levels of LDL-associated LPA while reducing albumin-associated LPA.
Additionally, we identified unexpected increases in a broad range of atherogenic lipoprotein
particle- associated lipid species when hyperlipidemic mice are put onto a western diet. These
studies provide new insights into how diet could influence coronary artery disease risk by
promoting increase in atherogenic lipoprotein associated LPA.
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