NAD ⁺ Levels Are Augmented in Aortic Tissue of ApoE ^−/− Mice by Dietary Omega-3 Fatty Acids

Abstract

Background: 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. Methods: Apolipoprotein E-deficient ( ApoE −/− ) 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. Results: 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. Conclusions: 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.

Targeted NAD+Delivery for Intimal Hyperplasia and Re-endothelialization: A Novel Anti-restenotic Therapy Approach

“…19 Disturbed NAD + homeostasis and decline of intracellular NAD + pool have been widely associated with vascular aging, hypertension, and atherosclerosis. [20][21][22] Serendipitously, our very own study as well as others demonstrate a pivotal role of NAD + repletion in protecting EC from sepsis-induced disease. 23 The role of NAD + in SMC, despite sparsely documented, is suggested to reinstate SMC phenotypic integrity, based on evidence derived from rodent models of aortic aneurysms.…”

“…22 Recent studies have highlighted the importance of the intracellular NAD + pool in maintaining vascular homeostasis. 20,24,42 NAD + deficiency has been linked to EC dysfunction, aortic aneurysm, aortic stiffness, hypertension, and other vascular pathologies. [42][43][44] The underlying mechanism behind NAD + 's role is multifaceted, including notable examples previously implicated in SMC/EC health and pathogenesis of IH, such as NAD + -dependent activation of sirtuin family (SIRTs) and deacetylation of substrate proteins, modulation of oxidative stress response, calcium signaling, and mitochondrial bioenergetics.…”

Effect of feeding high fat diets differing in fatty acid composition on oxidative stress markers and protein expression in mouse kidney

“…Defective NAD+ synthesis contributes to the development of kidney diseases, while maintaining NAD+ bioavailability may mitigate long-term profibrotic pathways leading to CKD (Ralto et al, 2020). Previous studies have shown that n-3 fatty acids may stimulate NAD+ biosynthesis in extrarenal tissues (Chi et al, 2022). Therefore, it is plausible that the high ALA levels in the LR diet could be responsible for attenuating fibrotic changes observed in the SFA and HR groups.…”

n-3 polyunsaturated fatty acids delay intervertebral disc degeneration by inhibiting nuclear receptor coactivator 4-mediated iron overload

“… 12 Previous studies have shown that n-3 PUFAs significantly inhibited the cellular senescence and tissue aging. 13 , 14 However, the relationship between n-3 PUFAs and senescence of the IVD cells still unknown.…”