Liu Yuan, Zhan Wenjing, Wang Lexun, Wang Weixuan
Traditional Chinese Medicine Research Institute, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China.
Guangdong Provincial Research Center of Integration of Traditional Chinese Medicine and Western Medicine in Metabolic Diseases, Guangdong Pharmaceutical University, Guangzhou, Guangdong Province, China.
Curr Med Chem. 2025;32(11):2202-2218. doi: 10.2174/0109298673293982240221050207.
Diabetic coronary heart disease is a global medical problem that poses a serious threat to human health, and its pathogenesis is complex and interconnected. Nicotinamide adenine dinucleotide (NAD) is an important small molecule used in the body that serves as a coenzyme in redox reactions and as a substrate for non-redox processes. NAD levels are highly controlled by various pathways, and increasing evidence has shown that NAD pathways, including NAD precursors and key enzymes involved in NAD synthesis and catabolism, exert both positive and negative effects on the pathogenesis of diabetic coronary heart disease. Thus, the mechanisms by which the NAD pathway acts in diabetic coronary heart disease require further investigation. This review first briefly introduces the current understanding of the intertwined pathological mechanisms of diabetic coronary heart disease, including insulin resistance, dyslipidemia, oxidative stress, chronic inflammation, and intestinal flora dysbiosis. Then, we mainly review the relationships between NAD pathways, such as nicotinic acid, tryptophan, the kynurenine pathway, nicotinamide phosphoribosyltransferase, and sirtuins, and the pathogenic mechanisms of diabetic coronary heart disease. Moreover, we discuss the potential of targeting NAD pathways in the prevention and treatment of diabetic coronary heart disease, which may provide important strategies to modulate its progression.
糖尿病性冠心病是一个全球性的医学问题,对人类健康构成严重威胁,其发病机制复杂且相互关联。烟酰胺腺嘌呤二核苷酸(NAD)是体内一种重要的小分子,在氧化还原反应中作为辅酶,在非氧化还原过程中作为底物。NAD水平受到多种途径的高度调控,越来越多的证据表明,NAD途径,包括NAD前体以及参与NAD合成和分解代谢的关键酶,对糖尿病性冠心病的发病机制既有正面影响也有负面影响。因此,NAD途径在糖尿病性冠心病中发挥作用的机制需要进一步研究。本综述首先简要介绍目前对糖尿病性冠心病相互交织的病理机制的理解,包括胰岛素抵抗、血脂异常、氧化应激、慢性炎症和肠道菌群失调。然后,我们主要综述NAD途径,如烟酸、色氨酸、犬尿氨酸途径、烟酰胺磷酸核糖转移酶和沉默调节蛋白等,与糖尿病性冠心病发病机制之间的关系。此外,我们还讨论了靶向NAD途径在糖尿病性冠心病预防和治疗中的潜力,这可能为调节其进展提供重要策略。