Bryan Raybuck

Circulating miRNA in patients with non-alcoholic fatty liver disease and coronary artery disease

Background Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and coronary artery disease (CAD) is the cardiac manifestation of metabolic syndrome. NAFLD is strongly linked to CAD and hepatic steatosis is an independent risk factor for CAD and cardiac mortality. The pathogenic mechanism underlying this association remains poorly understood. In this study, we explored expression of circulating microRNAs (miRNAs) in patients with NAFLD and associated CAD. Results When compared to patients with NAFLD without CAD, patients with NAFLD and CAD had lower circulating levels of miR-132 (0.24±0.16 vs 0.30±0.11, p=0.03), while the circulating levels of miR-143 were higher (0.96±0.90 vs 0.64±0.77, p=0.02). The levels in circulation demonstrated trends opposite to previously observed intracellular levels in patients with CAD. In obese patients with NAFLD, lower circulating levels of miR-145 (1.42±1.00 vs 2.41±1.80), miR-211 (41.26±20.40 vs 57.56±25.45), miR-146a (2.13±1.40 vs 2.90±1.36) and miR-30c (6.92±4.99 vs 11.0±6.92) were detected when compared to lean patients with NAFLD. For miR-161 (0.59±1.19 vs 0.15±0.14) and miR-241 (0.28±0.29 vs 0.16±0.13), higher circulatory levels were detected in the obese patients with NAFLD. These observations suggest altered circulating levels of miRNAs that may serve to balance intracellular levels of miRNA in target tissues. Additional studies examining paired samples of target and producing tissues as well as respective plasma samples will help delineate the regulatory circuits governing the secretion and the uptake of miRNA in multitissue diseases.

Markers of endothelial dysfunction in patients with non-alcoholic fatty liver disease and coronary artery disease.

Non‐alcoholic fatty liver disease (NAFLD) has been associated with coronary artery disease (CAD) and cardiac‐related mortality.

PATIENT-SPECIFIC 4D DIGITAL CLONING SIMULATION PREDICTS TRANSCATHETER AORTIC VALVE REPLACEMENT

Prediction of aortic root geometry and occurrence of paravalvular leak (PVL) following transcatheter aortic valve replacement (TAVR) is imprecise using current imaging modalities. A novel high resolution 4D computer modeling methodology was examined in order to investigate the mechanical interaction

139 CD45−CD34+ Circulating Progenitor Cells Levels Are Associated With the Presence of Coronary Artery Disease (CAD) in Patients With Nonalcoholic Fatty Liver Disease (NAFLD)

Background and Aim: Angiogenic growth factors (AGF) play a crucial role in regulating hematopoietic stem and progenitor cell homing and differentiation. Patients with NAFLD and CAD have lower levels of AGF (Elsheikh et al. DDW 2014). Thus, in this study we investigated the level and functions of circulating progenitor cells (CPC) in patients with NAFLD and CAD. Methods: We prospectively enrolled 82 patients undergoing elective coronary angiography. Each patient had fasting serum, clinical data and abdominal ultrasound (US). All US were read centrally using a standard protocol. NAFLD was defined as radiologic fatty liver in the absence of other causes of liver disease and excessive alcohol use. Patients were divided into NAFLD with CAD (n=24), NAFLD without CAD (n=13), only CAD (n= 31) and Non-NAFLD and Non-CAD (n=14). Circulating progenitor cells (CPC) were quantified by flow cytometry based on the expression of (CD34+, CD133+, CD34+ CD133+) in presence or absence of the hematopoietic marker (CD45). To study the functional capacity of CPC, colony-forming unit (CFU) assay was used. These include erythroid progenitors (burst-forming unit erythroid (BFU-E)); granulocyte/macrophage progenitors (CFU-granulocyte, macrophage (CFU-GM); and multi-potential progenitors (CFU-granulocyte, erythroid, macrophage, megakaryocyte (CFU-GEMM)). Results: The levels of the CD45-CD34+, CD45CD133+ and BFU-E were higher in NAFLD patients with CAD (median, 15%, 2% and 60 colonies, respectively) than NAFLD patients without CAD (median, 9%, 1% and 37 colonies , respectively, all p-values≤0.05). We also found that the levels of the CD45-CD133+ were higher in NAFLD patients with CAD (median, 15%) than patients with only CAD (median, 11%, p 25th quartile of CD45-CD34+, CD45-CD133+ and total CFU levels had the highest risk for CAD [OR: 7.00 (1.34-36.68), 5.00 (1.07-23.46) and 7.00 (1.10-44.61) respectively]. After age adjustment, only CD45-CD34+ circulating progenitor cells remain associated with increased risk of CAD in patients with NAFLD [OR: 8.71 (1.21-62.51)]. Conclusions: Our results indicate that, levels of circulating progenitor cells CD45-CD34+ may be associated with increased risk of CAD in NAFLD patients. Increased circulating progenitor cells levels could be due to the low levels of AGF leading to impaired homing and differentiation capacity.