The researchers also examined whether NAD+ supplementation can rescue VSMC senescence. Under healthy conditions, the intracellular NAD+ levels of whole aorta tissue were increased by nearly 50% in mice lacking CD38 compared with unmodified mice. Moreover, oral administration of NMN (300 mg/kg) to elevate NAD+ levels alleviated chemically-induced hypertension. In these hypertensive mice, the vascular media thickness, media-to-lumen ratio, and collagen deposition were reduced by 26%, 27%, and 30%, respectively, following injection with NMN (i.p., 10 mg/kg/dose).
In cell culture, the researchers pre-administered exogenous NAD+ (100 μM) to VSMCs and detected Ang II-induced cell senescence indicators. The results showed that the area positive for senescent cells was decreased by 54%. In addition, when the researchers increased the levels of CD38, the levels of senescence of VSMCs significantly increased. These results strongly supported that CD38 may be a potential pharmacological target for anti-senescence treatment.