Effects of Nicorandil on Inflammation, Apoptosis and Atherosclerotic Plaque Progression

作者：Max Lenz, Christoph Kaun, Konstantin A. Krychtiuk, Patrick Haider, Mira Brekalo, Nadine Maier, Laura Goederle, Christoph J. Binder, Kurt Huber, Christian Hengstenberg, Johann Wojta, Philipp J. Hohensinner, Walter S. Speidl · 发表于：Biomedicines · 年份：2021 · DOI：10.3390/biomedicines9020120 · 被引用次数：22 · 研究领域：Cardiac Ischemia and Reperfusion、Anesthesia and Neurotoxicity Research、Transplantation: Methods and Outcomes

Nicorandil, a balanced vasodilator, is used in the second-line therapy of angina pectoris. In this study, we aimed to illuminate the effects of nicorandil on inflammation, apoptosis, and atherosclerotic plaque progression. Twenty-five LDL-R -/- mice were fed a high-fat diet for 14 weeks. After 6 weeks mice were randomly allocated to treatment with nicorandil (10 mg/kg/day) or tap water. Nicorandil treatment led to a more stable plaque phenotype, displaying an increased thickness of the fibrous cap (p = 0.014), a significant reduction in cholesterol clefts (p = 0.045), and enhanced smooth muscle cell content (p = 0.009). In endothelial cells nicorandil did not reduce the induction of adhesion molecules or proinflammatory cytokines. In H2O2 challenged endothelial cells, pretreatment with nicorandil significantly reduced the percentage of late apoptotic/necrotic cells (p = 0.016) and the ratio of apoptotic to living cells (p = 0.036). Atherosclerotic lesions of animals treated with nicorandil exhibited a significantly decreased content of cleaved caspase-3 (p = 0.034), lower numbers of apoptotic nuclei (p = 0.040), and reduced 8-oxogunanine staining (p = 0.039), demonstrating a stabilizing effect of nicorandil in established atherosclerotic lesions. We suggest that nicorandil has a positive effect on atherosclerotic plaque stabilization by reducing apoptosis.