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Niacin receptor activation improves human microvascular endothelial cell angiogenic function during lipotoxicity
- Source :
- Atherosclerosis. 237:696-704
- Publication Year :
- 2014
- Publisher :
- Elsevier BV, 2014.
-
Abstract
- Objective : Niacin (nicotinic acid) as a monotherapy can reduce vascular disease risk, but its mechanism of action remains controversial, and may not be dependent on systemic lipid modifying effects. Niacin has recently been shown to improve endothelial function and vascular regeneration, independent of correcting dyslipidemia, in rodent models of vascular injury and metabolic disease. As a potential biosynthetic precursor for NAD + , niacin could elicit these vascular benefits through NAD + -dependent, sirtuin (SIRT) mediated responses. Alternatively, niacin may act through its receptor, GPR109A, to promote endothelial function, though endothelial cells are not known to express this receptor. We hypothesized that niacin directly improves endothelial cell function during exposure to lipotoxic conditions and sought to determine the potential mechanism(s) involved. Methods and results : Angiogenic function in excess palmitate was assessed by tube formation following treatment of human microvascular endothelial cells (HMVEC) with either a relatively low concentration of niacin (10 μM), or nicotinamide mononucleotide (NMN) (1 μM), a direct NAD + precursor. Although both niacin and NMN improved HMVEC tube formation during palmitate overload, only NMN increased cellular NAD + and SIRT1 activity. We further observed that HMVEC express GRP109A. Activation of this receptor with either acifran or MK-1903 recapitulated niacin-induced improvements in HMVEC tube formation, while GPR109A siRNA diminished the effect of niacin. Conclusion : Niacin, at a low concentration, improves HMVEC angiogenic function under lipotoxic conditions, likely independent of NAD + biosynthesis and SIRT1 activation, but rather through niacin receptor activation.
- Subjects :
- medicine.medical_specialty
Apoptosis
Receptors, Nicotinic
Biology
Niacin
Receptors, G-Protein-Coupled
Cell Movement
Internal medicine
medicine
Animals
Humans
Obesity
RNA, Small Interfering
Receptor
Aorta
Cells, Cultured
Nicotinamide Mononucleotide
Serum Albumin
Cell Proliferation
Nicotinamide mononucleotide
Metabolic Syndrome
Tube formation
Cell Death
Microcirculation
digestive, oral, and skin physiology
Endothelial Cells
nutritional and metabolic diseases
food and beverages
NAD
Immunohistochemistry
Lipids
Endothelial stem cell
Drug Combinations
Endocrinology
Gene Expression Regulation
Lipotoxicity
Sirtuin
biology.protein
Pyrazoles
Cattle
Proteoglycans
RNA Interference
Collagen
Laminin
NAD+ kinase
Cardiology and Cardiovascular Medicine
Protein Binding
Subjects
Details
- ISSN :
- 00219150
- Volume :
- 237
- Database :
- OpenAIRE
- Journal :
- Atherosclerosis
- Accession number :
- edsair.doi.dedup.....0a18b07b05c7aa4422cd5754643d9146