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2017 Cardiovascular Research Day Abstract Book

91 A patient with very

91 A patient with very high plasma level of high-density lipoprotein cholesterol (HDLc) and sudden cardiac arrest Wenliang Song, MD 1 • Ginger Milne, PhD 2 • John Fahrenholz, MD 3 • John McPherson, MD 1 • John Oates, MD 4 • Dan Roden, MD 1 • MacRae Linton, MD 1 1Cardiology, Vanderbilt University Medical Center • 2 Clinical Pharmacology, Vanderbilt University • 3Medicine, Vanderbilt University Medical Center • 4 Medicine, Vanderbilt University Postdoc Synopsis: A 58-year-old female with plasma HDLc of 110-150 mg/dL suffers from a very debilitating facial flushing for the past several years. She also had two episodes of sudden cardiac arrests. Purpose: To find a pathological condition that can explain the constellation of symptoms this patient has, which may provide important insights of HDL metabolism Methods: Extensive clinical work-ups to evaluate her constellation of symptoms and basic laboratory experiments including HPLC/MS/MS to evaluate specific biomarkers for rare orphan diseases Results: This patient's coronary angiogram was normal. However, acetylcholine challenge produced significant coronary spasm. Bone marrow biopsy excluded systemic mastocytosis. Urinary prostaglandin D2 metabolites increased after flushing attacks, which suggests the patient has a condition of mast cell activation syndrome. Her clinical constellation of symptoms mimic the niacin's pharmacological effect. Genetic investigation may shed lights on the mechanism of HDL metabolism and niacin's therapeutic effect. Conclusions: Isolated mast cell activation syndrome may cause coronary spasm. Rare gene mutation may be responsible for her condition. Future genetics investigation may shed lights on the mechanism of HDL metabolism. 107

92 Human Antigen R (HuR) Regulates Structure and Function of Brown Adipose Tissue Lindsey Lanzillotta 1 • Zach Taylor 1 • Kaila Yamamoto 1 • Sarah Anthony 1 • Shannon Jones 1 • George Yoshida 1 • A. Phillip Owens III, PhD 1 • Michael Tranter, PhD 1 1Internal Medicine, University of Cincinnati Graduate Student Human antigen R (HuR) is an RNA binding protein widely expressed throughout the body, including in both white (WAT) and brown (BAT) adipose tissue. Recent work from our lab has shown that adipocyte-specific HuR knockout (adipo-HuR-/-) mice gain less weight following a high fat diet (HFD) compared to wild type (WT) controls. In this study, we focused on the role of HuR deletion on the function of BAT, which mediates non-shivering thermogenesis. Histological analysis revealed that, while the BAT of the chow fed adipo-HuR-/- mice appeared normal, the BAT of the HFD fed adipo-HuR-/- mice appears less dense with a cell size that more closely resembles WAT. Upon further examination of BAT function, our results show that, when subjected to cold stress (4C), adipo-HuR-/- mice are less cold tolerant compared to their WT counterparts . We also show that, compared to the WT mice, adipo-HuR-/- mice have decreased mitochondrial density and expression of uncoupling protein-1 (UCP-1) in their BAT. This may be caused by a HuR-dependent decrease in expression of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1a), which plays a key role in mitochondrial biogenesis and is upregulated during exposure to cold (4C). In conclusion, our results indicate that HuR regulates both the structure and function of BAT, at least in part through modulation of PGC-1a mRNA expression. Support or Funding Information: This work was supported by a University of Cincinnati Heart, Lung, and Vascular Institute Near Horizons Grant (MT, APO). 108

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