Niacin inhibits vascular oxidative stress, redox-sensitive genes, and monocyte adhesion to human aortic endothelial cells.
In pharmacological doses, nicotinic acid (niacin) reduces myocardial infarction, stroke and atherosclerosis. The beneficial effects of niacin on lipoproteins are thought to mediate these effects. We hypothesized that niacin inhibits oxidative stress and redox-sensitive inflammatory genes that play a critical role in early atherogenesis. In cultured human aortic endothelial cells (HAEC), niacin increased nicotinamide adenine dinucleotide phosphate (NAD(P)H) levels by 54% and reduced glutathione (GSH) by 98%. Niacin inhibited: (a) angiotensin II (ANG II)-induced reactive oxygen species (ROS) production by 24-86%, (b) low density lipoprotein (LDL) oxidation by 60%, (c) tumor necrosis factor alpha (TNF-alpha)-induced NF-kappaB activation by 46%, vascular cell adhesion molecule-1 (VCAM-1) by 77-93%, monocyte chemotactic protein-1 (MCP-1) secretion by 34-124%, and (d) in a functional assay TNF-alpha-induced monocyte adhesion to HAEC (41-54%). These findings indicate for the first time that niacin inhibits vascular inflammation by decreasing endothelial ROS production and subsequent LDL oxidation and inflammatory cytokine production, key events involved in atherogenesis. Initial data presented herein support the novel concept that niacin has vascular anti-inflammatory and potentially anti-atherosclerotic properties independent of its effects on lipid regulation.
Ganji
Shobha H
SH
Atherosclerosis Research Center, Department of Veterans Affairs Healthcare System, Long Beach, CA 90822, United States.
Qin
Shucun
S
Zhang
Linhua
L
Kamanna
Vaijinath S
VS
Kashyap
Moti L
ML
D001011:Aorta / Q000166:cytology; D002448:Cell Adhesion; D002478:Cells, Cultured; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000473:pathology; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008077:Lipoproteins, LDL / Q000378:metabolism; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D009525:Niacin / Q000494:pharmacology*; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology
D008077:Lipoproteins, LDL; D017382:Reactive Oxygen Species; D019010:Vascular Cell Adhesion Molecule-1; D014665:Vasodilator Agents; D009525:Niacin; D005978:Glutathione