Abstract 16245: Lactobacillus Plantarum Probiotic Preserves Endothelial Function and Diastolic Performance in the Ischemic Myocardium Through Redox Nrf2 Antioxidant Signaling

Abstract

Introduction: Oxidative homeostasis is critical to the viability of the vascular endothelium. Nrf2 is a redox-sensitive transcription factor that induces several cyto-protective and antioxidant genes in response to stress. Lactobacillus plantarum , a probiotic bacterium, can convert caffeic acid to 4-vinyl catechol, a natural activator of Nrf2. Hypothesis: We hypothesized that a diet consisting of applesauce, which is rich in caffeic acid, supplemented with L. plantarum can generate sufficient concentrations of 4-vinyl catechol to enhance Nrf2 activity and thereby ameliorate ischemic injury in the myocardium. Methods: Fourteen Yorkshire swine received a standard diet with 10 ml of 10% ethanol vehicle for three weeks (NDC; n=7); the treatment group was additionally fed unsweetened applesauce with L. plantarum supplements (ND-LP; n=7). Subsequently, an ameroid constrictor was placed around their left coronary circumflex artery (Lcx). Dietary regimens were continued for a period of fourteen weeks thereafter. Finally, cardiac function, myocardial perfusion, vascular density, and molecular signaling were examined. Results: The L. plantarum -applesauce diet upregulated Nrf2 signaling in the ischemic myocardium, thus inducing several antioxidant enzymes including heme oxygenase1 (HO-1), NADPH dehydrogenase quinone 1 (NQO-1), and thioredoxin reductase (TRXR-1). Reduced ischemic myocardial density of alpha smooth muscle actin (αSMA) and improved myocardial relaxation seen in the treatment cohort may reflect less ischemic fibrosis. Nrf2 activation increased expression of endothelial nitric oxide synthase (eNOS) and lowered concentrations of asymmetric dimethyl arginine (ADMA) in ischemic myocardial tissue, but did not significantly affect blood flow nor endothelial cell density. The expression of hypoxia inducible factor 1α (HIF-1α) and phosphorylated MAPK (pMAPK) was reduced in ischemic myocardial lysates from treatment animals. Conclusions: Dietary supplementation with L. plantarum and caffeic acid is a safe and effective mean of enhancing Nrf2 activity, which supported endothelial function and diastolic performance, while diminishing hypoxic stimulation of collateral vessel formation in the ischemic myocardium.