Abstract | BACKGROUND: Diabetic patients suffer from undesired intimal hyperplasia after angioplasty. Nicorandil has a trend to reduce the rate of target lesion revascularization. However, whether nicorandil inhibits intimal hyperplasia and the possible mechanisms underlying it remain to be determined. We aimed at assessing the effect of nicorandil on intimal hyperplasia in diabetic rats. METHODS: RESULTS: Intimal hyperplasia significantly increased 14 days after balloon injury in diabetic rats (p < 0.01). Nicorandil inhibited intima development, reduced inflammation and prevented cell proliferation in balloon-injured arteries (p < 0.01). The protective effects of nicorandil were reversed by 5-HD (p < 0.05). εPKC was activated in balloon-injured arteries (p < 0.01). Nicorandil inhibited εPKC activation by opening mitoKATP channel. Perivascular delivery of εPKC siRNA inhibited intimal hyperplasia, inflammation and cell proliferation (p < 0.01). High glucose-induced VSMCs proliferation and migration were inhibited by nicorandil. εPKC activation induced by high glucose was also inhibited by nicorandil and that is partially reversed by 5-HD. εPKC knockdown prevented VSMCs proliferation and migration (p < 0.01). CONCLUSIONS: Our study demonstrates that nicorandil inhibits intimal hyperplasia in balloon-injured arteries in diabetic rats. Nicorandil also prevents VSMCs proliferation and migration induced by high glucose. The beneficial effect of nicorandil is conducted via opening mitoKATP channel and inhibiting εPKC activation.
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Authors | Ying Qian Zhang, Feng Tian, Ying Zhou, Yun Dai Chen, Bo Li, Qiang Ma, Ying Zhang |
Journal | Cardiovascular diabetology
(Cardiovasc Diabetol)
Vol. 15
Pg. 62
(Apr 08 2016)
ISSN: 1475-2840 [Electronic] England |
PMID | 27059601
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
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Topics |
- Angioplasty, Balloon
(methods)
- Animals
- Carotid Arteries
(drug effects, pathology)
- Carotid Artery Injuries
(drug therapy, metabolism)
- Cell Movement
(drug effects)
- Cell Proliferation
(drug effects)
- Diabetes Mellitus, Experimental
(drug therapy, metabolism)
- Endothelium, Vascular
(drug effects, metabolism)
- Hyperplasia
(drug therapy)
- Male
- Muscle, Smooth, Vascular
(drug effects)
- Nicorandil
(pharmacology)
- Rats, Sprague-Dawley
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