The role of lncRNA CRNDE in obesity‐associated endothelial dysfunction

Abstract

Obesity, a risk factor for type II diabetes and cardiovascular disease affects 35.7% of the U.S. population and costs approximately $210 billion per year. Endothelial cells (ECs) are cells that line blood vessels, are important in signaling and transport and have been implicated in obesity. The role of long non‐coding RNA (lncRNA) in regulating endothelial function, especially under disease conditions, has been understudied. In an RNA‐seq analysis of palmitate‐treated ECs, the lncRNA Colorectal Neoplasia Differentially Expressed (CRNDE) was determined to be upregulated. The purpose of this study is to determine the role of CRNDE in EC function through examination of various signaling pathways and exploring how obesogenic stimuli induce CRNDE expression. To determine the effect of obesogenic stimuli on CRNDE expression, HUVECs were treated with albumin‐conjugated palmitic acids or albumin for 4 or 12 hours and CRNDE expression was determined by qPCR. CRNDE is significantly increased in palmitic acid‐treated HUVECs after 12 hours compared with cells treated with albumin. Bioinformatic analysis of CRNDE and its promoter reveals the presence of p53 binding sites at CRNDE promoter which mediate the induction of CRNDE. To test this, CRNDE expression will be examined in HUVECs in the presence or absence of p53 knockdown. Chromatin immunoprecipitation will be used to determine the binding of p53 at the CRNDE promoter in HUVECs. Loss‐of‐ and gain‐of‐function studies will be performed to examine the signaling pathway that is regulated by CRNDE. Understanding the role of CRNDE in obesity‐associated endothelial dysfunction could provide new targets to reduce vascular complications associated with obesity and diabetes.Support or Funding InformationUCAREThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.