Differences in Extracellular NAD+ and NMN Metabolism on the Surface of Vascular Endothelial Cells

Abstract

The disruption of the metabolism of extracellular NAD+ and NMN may affect related signaling cascades and pathologies, such as cardiovascular or respiratory system diseases. We aimed to study NAD+ and NMN hydrolysis on surface endothelial cells of diverse origins and with genetically modified nucleotide catabolism pathways. We tested lung endothelial cells isolated from C57BL/6 J wild-type (WT) and C57BL/6 J CD73 knockout (CD73 KO) mice, the transfected porcine iliac artery endothelial cell line (PIEC) with the human E5NT gene for CD73 (PIEC CD73), and a mock-transfected control (PIEC MOCK), as well as HMEC-1 and H5V cells. Substrate conversion into the product was followed by high-performance liquid chromatography (HPLC). We showed profound differences in extracellular NAD+ and NMN metabolism related to the vessel origin, species diversity, and type of culture. We also confirmed the involvement of CD38 and CD73 in NAD+ and NMN cleavage.

Translational Aspects of Cardiovascular Biology: From Bench to Bedside

“…The Special Issue opens with three basic research papers, which investigate endothelial The first article shows that a specific non-coding RNA, microRNA-4432, is able to specifically target the gene encoding for fibroblast growth factor binding protein 1 (FGFBP1) in human brain microvascular endothelial cells, and this paper demonstrates that this microRNA significantly reduces endothelial oxidative stress, a well-established feature hypertension [1]. The second study provides a demonstration of the extracellular metabolism of nicotinamide adenine dinucleotide (NAD+) and nicotinamide mononucleotide (NMN), multifunctional metabolites involved in a number of cellular processes, and which is vastly different in its expression in the vascular endothelium obtained from different species and locations [2]. The third paper, instead, deals with the functions and intracellular mechanisms of endothelial cells in human liver grafts [3].…”