Niacin Inhibits Vascular Inflammation via the Induction of Heme Oxygenase-1
Background—Heme oxygenase-1 (HO-1) is a cytoprotective protein whose expression is consistently associated with therapeutic benefits in a number of pathological conditions such as atherosclerotic vascular disease and inflammation. Niacin is a pleiotropic drug which slows the progression of coronary artery disease and increases serum levels of the HO-1 enzymatic product, bilirubin. This study asks if the cardioprotective properties of niacin involve the induction of HO-1.
Methods and Results—New Zealand White rabbits received chow, or chow supplemented with 0.6% (wt/wt) niacin, for 2 weeks. Acute vascular inflammation was induced in the animals by placing a non-occlusive silastic collar around the left common carotid artery. At 24 h post-collar implantation, serum bilirubin, and vascular, liver and spleen HO-1 mRNA levels were significantly increased. Vascular inflammation was decreased in the niacin-supplemented animals compared with control. Treatment of the animals with tin protoporphyrin-IX (SnPP), a global HO inhibitor, or HO-1 siRNA to knock down carotid artery HO-1, attenuated the ability of niacin to inhibit vascular inflammation. Treatment of cultured human coronary artery endothelial cells (HCAECs) with niacin increased HO-1 expression by activating the nuclear factor-E2-related factor 2 (Nrf2)/p38 mitogen-activated protein kinase signaling pathway, and inhibiting tumor necrosis factor-α-induced endothelial inflammation. The anti-inflammatory effects of niacin in HCAECs were mimicked by bilirubin, and abolished by incubation with SnPP and knock down of Nrf2.
Conclusions—Niacin activates HO-1 in vivo and in vitro. Induction of HO-1 may be partly responsible for the vascular protective properties of niacin.
- Received June 29, 2011.
- Accepted November 11, 2011.
- Copyright © 2011, American Heart Association, Inc. All rights reserved. Unauthorized use prohibited