2017 Cardiovascular Research Day Abstract Book

26
Vascular inflammation induced expression of lipid phosphate phosphatase
Kavya Balaji 1 • Patrick Van Hoose, PhD 1 • Andrew Morris, PhD 1 • Susan Smyth, MD, PhD 1
1Cardiovascular Research Center, University of Kentucky
Undergraduate
Lipid phosphate phosphatase 3 (PLPP3) is a polymorphic gene that is a member of the phosphatidic
acid phosphatase family. It encodes for the cell surface enzyme, lipid phosphate phosphatase 3
(LPP3) that regulates lysophosphatidic acid (LPA) and sphingosine-1-phosphate (S1P) availability
and signaling. Genome wide association studies in humans identified heritable single nucleotide
polymorphisms (SNPs) in PLPP3 that predicts coronary artery disease risk independently of
traditional risk factors (odds ratio, 1.17; P=3.81×10–19). PLPP3 is dynamically regulated during
vascular inflammation and the risk allele reduces gene expression by disrupting binding of CCAAT
enhancer binding protein beta (CEBPβ). However, other mechanisms may control dynamic
regulation of PLPP3. The USC Genome Browser identifies potential target sequences for NFκB
responsive elements in the PLPP3 promoter, including three potential RelA (p65) binding sites.
Hypothesis: These observations led to the hypothesis that angiotensin II, an inducer of vascular
inflammation could regulate of PLPP3.
Methods: Coronary human smooth muscle cells (caHSMCs) were treated for 12, 24, 48 and 72hrs
hours with 1 M angiotensin II (ATII) in the presence or absence of parthenolide. Following
treatment PLPP3 and p65 gene expression was examined.
Results: The time course treatment of ATII revealed 72hr treatment upregulated PLPP3 gene
expression in caHSMCs and this upregulation of PLPP3 was inhibited in the presence of
parthenolide, an inhibitor of IκBα degradation.
Conclusion: These observations suggest possible regulation of PLPP3 via an angiotensin II-NFkB
dependent pathway, which may be important in the context of vascular disease.
42