Figure 2

Figure 2 : 

Therapeutic potential of compounds modulating oxidized nicotinamide adenine dinucleotide (NAD+) homeostasis and signalling in heart failure. Vitamin B3 (nicotinic acid [NA] and NA derivatives, such as acipimox, nicotinamide [NAM] and nicotinamide riboside [NR]) and nicotinamide mononucleotide (NMN) can be used to stimulate NAD+ synthesis and oxidative metabolism. NAM is not only a precursor of NAD+ but also an inhibitor of sirtuins, so its use maybe counterproductive. Poly(adenosine diphosphate-ribose) polymerase (PARP) inhibitors (e.g. olaparib, veliparib, niraparib, L-2286 and AG-690/11026014) can limit the high NAD+ consumption by PARP1 and have been shown to be beneficial in preclinical models. Alternatively, inhibitors of the other major NAD+ hydrolase CD38 (e.g. 4-amino-8-quinoline carboxamide compounds, daratumumab [HuMax®-CD38; Genmab, Copenhagen, Denmark] a human immunoglobulin G1κ monoclonal antibody) could help to maintain NAD concentrations in the myocardium, although they have not been tested in preclinical models of heart failure as yet. Sirtuins consume NAD+, but at moderate level and, overall, their action is thought to be protective in the context of pathological cardiac remodelling. This hypothesis is supported by the beneficial action of sirtuin activators on cardiovascular health (e.g. resveratrol, SRT1460, SRT1720, SRT2183, STAC-5, STAC-9, STAC-10). Importantly, a beneficial side effect of sirtuin-1 (SIRT1) activators could be repression of deleterious PARP1 activity. Ca2+: calcium.