Journal
ATHEROSCLEROSIS
Volume 214, Issue 2, Pages 415-421Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.atherosclerosis.2010.11.032
Keywords
Vasodilation; Atherosclerosis; Coronary disease; Plaque
Funding
- Ministry of Education, Science, and Culture, Japan [C-18590780]
- [20890170]
- Grants-in-Aid for Scientific Research [22790713, 18590780] Funding Source: KAKEN
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Objective: The Impact of Nicorandil in Angina (IONA) trial demonstrated that the use of nicorandil, an anti-anginal drug, reduced future cardiovascular events in patients with stable angina. We hypothesized that nicorandil has beneficial effects on coronary arterial plaque characteristics and atherosclerogenesis. Methods and Results: Preintervention intravascular ultrasound-virtual histology was performed prospectively in 65 consecutive patients with stable angina pectoris. There were no differences in coronary risk factors between the nicorandil (n = 16) and non-nicorandil (n = 49) groups. However, the nicorandil group demonstrated a larger %fibrous tissue (68 +/- 10 vs. 62 +/- 11%, P = 0.049) and a smaller %necrotic core tissue (11 +/- 7 vs. 16 +/- 10%, P = 0.049) compared with the non-nicorandil group. Multiple regression analysis showed that %necrotic core tissue (P = 0.045) was negatively and %fibrous tissue (P = 0.026) was positively associated with the use of nicorandil independent of statin use. We also analyzed the effect of nicorandil on atherosclerotic lesion formation in a mouse model of atherosclerosis. Lipid profiles were unaffected, but the area of atherosclerotic lesion and plaque necrosis were significantly reduced following 8-week nicorandil treatment in ApoE-deficient mice fed an atherogenic diet. Nicorandil significantly reduced the expression levels of endoplasmic reticulum stress markers, C/EBP homologous protein (CHOP) and glucose regulated protein/BiP (GRP78) in atherosclerotic lesions. Nicorandil significantly attenuated tunicamycin-induced CHOP upregulation in cultured THP-1 macrophages. Conclusions: Nicorandil exerts its anti-atherogenic effect by mechanisms different from those of statins. Long-term nicorandil treatment is a potentially suitable second-line prevention therapy for patients with coronary artery disease. (C) 2010 Elsevier Ireland Ltd. All rights reserved.
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