Department of Cellular and Molecular Anatomy (D.H.C., T.K., A.I., M.M.H., A.S.M.W., M.A.M., M.N., T.S., M.S.), Hamamatsu University School of Medicine, Shizuoka, Japan.
International Mass Imaging Center (T.K., M.N., T.S., M.S.), Hamamatsu University School of Medicine, Shizuoka, Japan.
Arterioscler Thromb Vasc Biol. 2022 Apr;42(4):395-406. doi: 10.1161/ATVBAHA.121.317166. Epub 2022 Feb 10.
Maintaining bioenergetic homeostasis provides a means to reduce the risk of cardiovascular events during chronological aging. Nicotinamide adenine dinucleotide (NAD) acts as a signaling molecule, and its levels were used to govern several biological pathways, for example, promoting angiogenesis by SIRT1 (sirtuin 1)-mediated inhibition of Notch signaling to rejuvenate capillary density of old-aged mice. NAD modulation shows promise in the vascular remodeling of endothelial cells. However, NAD distribution in atherosclerotic regions remains uncharacterized. Omega-3 polyunsaturated fatty acids consumption, such as docosahexaenoic acid and eicosapentaenoic acid, might increase the abundance of cofactors in blood vessels due to omega-3 polyunsaturated fatty acids metabolism.
Apolipoprotein E-deficient () mice were fed a Western diet, and the omega-3 polyunsaturated fatty acids-treated groups were supplemented with docosahexaenoic acid (1%, w/w) or eicosapentaenoic acid (1%, w/w) for 3 weeks. Desorption electrospray ionization mass spectrometry imaging was exploited to detect exogenous and endogenous NAD imaging.
NAD, NADH, NADP, NADPH, FAD, FADH, and nicotinic acid adenine dinucleotide of the aortic arches were detected higher in the omega-3 polyunsaturated fatty acids-treated mice than the nontreated control. Comparing the distribution in the outer and inner layers of the arterial walls, only NADPH was detected slightly higher in the outer part in eicosapentaenoic acid-treated mice.
Supplementation of adding docosahexaenoic acid or eicosapentaenoic acid to the Western diet led to a higher NAD, FAD, and their metabolites in the aortic arch. Considering the pleiotropic roles of NAD in biology, this result serves as a beneficial therapeutic strategy in the animal model counter to pathological conditions.
维持生物能量稳态提供了一种降低心血管事件风险的方法，这种风险随着年龄的增长而增加。烟酰胺腺嘌呤二核苷酸 (NAD) 作为一种信号分子，其水平用于控制多种生物途径，例如，通过 SIRT1（沉默调节蛋白 1）介导的 Notch 信号抑制来促进血管生成，从而恢复老年小鼠毛细血管密度。NAD 调节有望改善内皮细胞的血管重塑。然而，动脉粥样硬化区域的 NAD 分布仍未得到描述。ω-3 多不饱和脂肪酸（如二十二碳六烯酸和二十碳五烯酸）的消耗可能会增加血管中辅助因子的丰度，这是由于 ω-3 多不饱和脂肪酸的代谢。
载脂蛋白 E 缺陷（）小鼠喂食西方饮食，ω-3 多不饱和脂肪酸处理组用二十二碳六烯酸（1%，w/w）或二十碳五烯酸（1%，w/w）补充 3 周。利用解吸电喷雾电离质谱成像检测外源性和内源性 NAD 成像。
与未处理的对照组相比，主动脉弓中外源和内源 NAD、NADH、NADP、NADPH、FAD、FADH 和烟酰胺腺嘌呤二核苷酸的含量在 ω-3 多不饱和脂肪酸处理组中更高。比较动脉壁内外层的分布，只有在外层的 ω-3 多不饱和脂肪酸处理组中，NADPH 的含量略高。
在西方饮食中添加二十二碳六烯酸或二十碳五烯酸补充剂可导致主动脉弓中 NAD、FAD 及其代谢物含量升高。考虑到 NAD 在生物学中的多效性作用，这一结果为动物模型中的病理条件提供了有益的治疗策略。
