NAD Pathways in Diabetic Coronary Heart Disease: Unveiling the Key Players

Abstract: 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.