Unraveling the Molecular Mechanisms of SIRT7 in Angiogenesis: Insights from Substrate Clues

Abstract

Angiogenesis, a vital physiological or pathological process regulated by complex molecular networks, is widely implicated in organismal development and the pathogenesis of various diseases. SIRT7, a member of the Sirtuin family of nicotinamide adenine dinucleotide + (NAD⁺) dependent deacetylases, plays crucial roles in cellular processes such as transcriptional regulation, cell metabolism, cell proliferation, and genome stability maintenance. Characterized by its enzymatic activities, SIRT7 targets an array of substrates, several of which exert regulatory effects on angiogenesis. Experimental evidence from in vitro and in vivo studies consistently demonstrates the effects of SIRT7 in modulating angiogenesis, mediated through various molecular mechanisms. Consequently, understanding the regulatory role of SIRT7 in angiogenesis holds significant promise, offering novel avenues for therapeutic interventions targeting either SIRT7 or angiogenesis. This review delineates the putative molecular mechanisms by which SIRT7 regulates angiogenesis, taking its substrates as a clue, endeavoring to elucidate experimental observations by integrating knowledge of SIRT7 substrates and established angiogenenic mechanisms.

Keywords: SIRT7; angiogenesis; molecular mechanism; substrate; vascular endothelial growth factor.

Figure 1

Summary of this review. Further exploration into the hypothetical mechanisms underlying the angiogenic regulation of SIRT7 not only elucidates previous experimental findings but also informs the design of future experiments. SIRT7 orchestrates modifications on its substrates, thereby regulating angiogenesis via multiple angiogenic signaling pathways. Various studies have demonstrated the role of SIRT7 in modulating angiogenesis in both in vitro and in vivo models. (Created with BioRender.com).