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2017 Cardiovascular Research Day Abstract Book

87 Perioperative high

87 Perioperative high density lipoprotein particle changes and the risk of acute kidney injury after cardiac surgery Loren Smith, MD, PhD 1 • Derek Smith, PhD 2 • Alan Remaley, MD, PhD 3 • MacRae Linton, MD 4 • Frederic Billings IV, MD 5 1Anesthesiology, Vanderbilt University Medical Center • 2 Biostatistics, Vanderbilt University Medical Center • 3 National Heart, Lung, and Blood Institute, National Institutes of Health • 4Medicine and Pharmacology, Vanderbilt University Medical Center • 5 Anesthesiology and Medicine, Vanderbilt University Medical Center Faculty Acute kidney injury (AKI) after cardiac surgery occurs in up to 30% of patients and increases the risk of postoperative myocardial infarction and death. No effective treatments exist. Increased intraoperative oxidative stress independently predicts AKI after cardiac surgery. High density lipoproteins (HDL) have anti-oxidant capacity. We hypothesize that perioperative HDL cholesterol concentration (HDL-C), HDL particle concentration (HDL-P) and HDL composition are associated with the risk of postoperative AKI. We analyzed data from a prospective, 393-subject trial of perioperative atorvastatin to prevent AKI after cardiac surgery. Statin-using patients were randomized to placebo or 80mg atorvastatin the morning of surgery and 40mg on postoperative day 1. Stain-naïve patients were randomized to placebo or 80mg the day prior to surgery and 40mg daily thereafter during hospitalization. The associations between 1) HDL-C, 2) small HDL particle concentration, and 3) the change in HDL-P from anesthetic induction to postoperative day two with maximum serum creatinine change from baseline in the first 48 postoperative hours were assessed using two-component latent variable mixture models adjusted for known AKI risk factors. Regression analyses assessed interactions of chronic statin use, perioperative atorvastatin treatment, and HDL-C on AKI risk. We quantified HDL particle size by NMR Lipoprofile test in 90 subjects. HDL-C and HDL-P change over time were assessed with mixed effects models adjusted for AKI risk factors. We quantified myeloperoxidase (MPO) activity of apolipoprotein B-depleted serum in 30 subjects using a bioluminescence assay. A higher preoperative HDL-C was independently associated with a decreased postoperative serum creatinine change (p=0.02). The association between a high HDL-C and an attenuated increase in serum creatinine was strongest in chronic statin-using patients (p=0.008) and was enhanced with perioperative atorvastatin treatment (p=0.004) and increasing chronic statin dose (p=0.003). HDL- C did not change during the perioperative period (p=0.60), however, HDL-P decreased (p

88 The Effects of Hypercholesterolemia on Wound Healing and Endothelial Angiogenic Properties Yedida Bogachkov 1 • Lin Chen, MD, PhD 2 • Myung-Jin Oh, PhD 3 • Luisa A. DiPietro, PhD 2 • Irena Levitan, PhD 4 1Pharmacology, University of Illinois at Chicago • 2 Periodontics, University of Illinois at Chicago • 3Medicine, University of Chicago • 4 Pulmonary, Critical Care, Sleep and Allergy, University of Illinois at Chicago Graduate Student Nearly 31 million adults in the US have elevated total cholesterol levels over 240 mg/dL, and almost 32% of US adults have LDL cholesterol levels of 200mg/dL or above. Our study focuses on the impact of dyslipidemia on wound healing and wound angiogenesis. Using ApoE-/- mice, a known dyslipidemic model and a skin punch biopsy wound healing assay, we show that ApoE -/- mice show significantly delayed wound closure on days 2-7 post-wounding compared to control mice. These same ApoE-/- also display significantly decreased angiogenesis on days 10 and 14 post wounding, based on PECAM staining for endothelial cells, indicative of endothelial cell infiltration of the wound bed and new blood vessel growth. Furthermore, macrophage infiltration is also reduced. This significant suppression of wound angiogenesis is also seen when LDL is directly applied to the wounds via subcutaneous injections on C57BL6 mice. Additionally, using a matrigel plug assay, we show significantly suppressed angiogenesis in C57BL6 mice fed a Western Diet for 40 weeks. These results utilize an Isolectin B4 probe, which is indicative of endothelial cell infiltration into the matrigel plug and new blood vessel growth. Finally, in vitro studies on human aortic endothelial cells were pursued showing LDL significantly decreases endothelial cell proliferation, whereas its oxidized form, oxLDL, shows an increase in proliferation. In sum, we have shown in vivo that hypercholesterolemic mice have a decreased angiogenic potential, and in vitro, excess LDL leads to a decrease in angiogenic potential of aortic endothelial cells. 104

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