The Role of Sirtuin-1 (SIRT1) in the Physiology and Pathophysiology of the Human Placenta

Abstract

Sirtuins, especially SIRT1, play a significant role in regulating inflammatory response, autophagy, and cell response to oxidative stress. Since their discovery, sirtuins have been regarded as anti-ageing and longevity-promoting enzymes. Sirtuin-regulated processes seem to participate in the most prevalent placental pathologies, such as pre-eclampsia. Furthermore, more and more research studies indicate that SIRT1 may prevent pre-eclampsia development or at least alleviate its manifestations. Having considered this, we reviewed recent studies on the role of sirtuins, especially SIRT1, in processes determining normal or abnormal development and functioning of the placenta.

Keywords: PPARγ; SIRT1; SIRT1/PPARγ signaling; human placenta; peroxisome proliferator-activated receptor γ; placental pathophysiology; placental physiology; pre-eclampsia; sirtuin-1; sirtuins.

Figure 1

Mechanisms of the beneficial effect of the natural sirtuin-1 activator resveratrol at the endothelium level and trophoblast level under oxidative stress (e.g., accompanying pre-eclampsia) [7,101,102,103,104,105].

Figure 2

Beneficial effects of SIRT1 on vascular endothelial cells in pre-eclampsia: limiting oxidative stress, inflammatory response, and cellular ageing.

Figure 3

Mechanisms of action of SIRT1 towards maintaining the homeostasis of both endothelial cells and trophoblast by promoting autophagy.