Department of Physiology and Pharmacology Schulich School of Medicine and Dentistry Western University London Ontario Canada N6A 5C1.
Robarts Research Institute Western University London Ontario Canada N6A 5C1.
Pharmacol Res Perspect. 2016 Apr 14;4(3):e00233. doi: 10.1002/prp2.233. eCollection 2016 Jun.
Niacin can reduce vascular disease risk in individuals with metabolic syndrome, but in light of recent large randomized controlled trials outcomes, its biological actions and clinical utility remain controversial. Niacin can improve endothelial function, vascular inflammation, and vascular regeneration, independent of correcting dyslipidemia, in various lean rodent models of vascular injury. Here, we tested whether niacin could directly improve endothelial cell angiogenic function during combined exposure to excess fatty acids and hypoxia, and whether intervention with niacin during continued feeding of western diet could improve revascularization and functional recovery in obese, hyperlipidemic mice with peripheral ischemia. Treatment with niacin (10 μmol/L) increased human microvascular endothelial cell angiogenic function during exposure to high fatty acids and hypoxia (2% oxygen), as determined by tube formation on Matrigel. To assess revascularization in vivo, we used western diet-induced obese mice with unilateral hind limb femoral artery ligation and excision. Treatment for 14 days postinjury with once daily i.p. injections of a low dose of niacin (50 mg/kg) improved recovery of hind limb use, in association with enhanced revascularization and decreased inflammation of the tibialis anterior muscle. These effects were concomitant with decreased plasma triglycerides, but not increased plasma apoAI. Thus, niacin improves endothelial tube formation under lipotoxic and hypoxic conditions, and moreover, promotes revascularization and functional hind limb recovery following ischemic injury in diet-induced obese mice with hyperlipidemia. These data may have implications for niacin therapy in the treatment of peripheral ischemic vascular disease associated with metabolic syndrome.
烟酸可以降低代谢综合征患者的血管疾病风险，但鉴于最近大型随机对照试验的结果，其生物学作用和临床应用仍存在争议。烟酸可以改善内皮功能、血管炎症和血管再生，而与纠正血脂异常无关，在各种瘦鼠血管损伤模型中都是如此。在这里，我们测试了烟酸是否可以在同时暴露于过量脂肪酸和缺氧的情况下直接改善内皮细胞的血管生成功能，以及在继续给予西方饮食的情况下，烟酸干预是否可以改善肥胖、高血脂、外周缺血小鼠的血管再生和功能恢复。用 10 μmol/L 的烟酸处理可增加人微血管内皮细胞在高脂肪酸和低氧（2%氧气）暴露下的血管生成功能，这可通过在 Matrigel 上形成管腔来确定。为了评估体内的血管再生，我们使用了单侧后肢股动脉结扎和切除的西方饮食诱导肥胖小鼠。在损伤后 14 天内每天一次腹腔注射低剂量烟酸（50mg/kg）治疗可改善后肢使用的恢复，与增强的血管再生和减少的胫骨前肌炎症相关。这些作用与血浆甘油三酯降低有关，但与血浆 apoAI 增加无关。因此，烟酸可以改善脂毒性和缺氧条件下的内皮管形成，并且可以促进饮食诱导的肥胖高脂血症小鼠缺血性损伤后血管再生和功能后肢恢复。这些数据可能对治疗与代谢综合征相关的外周缺血性血管疾病的烟酸治疗具有重要意义。
