Acacetin Protects Against High Glucose-Induced Endothelial Cells Injury by Preserving Mitochondrial Function via Activating Sirt1/Sirt3/AMPK Signals

Abstract

The strategy of decreasing atherosclerotic cardiovascular disorder is imperative for reducing premature death and improving quality of life in patients with diabetes mellitus. The aim of this study was to investigate whether the natural flavone acacetin could protect against endothelial injury induced by high glucose and attenuate diabetes-accelerated atherosclerosis in streptozotocin-(STZ) induced diabetic ApoE−/− mice model. It was found that in human umbilical vein endothelial cells (HUVECs) cultured with normal 5.5 mM or high 33 mM glucose, acacetin (0.3–3 μM) exerted strong cytoprotective effects by reversing high glucose-induced viability reduction and reducing apoptosis and excess production of intracellular reactive oxygen species (ROS) and malondialdehyde in a concentration-dependent manner. Acacetin countered high glucose-induced depolarization of mitochondrial membrane potential and reduction of ATP product and mitoBcl-2/mitoBax ratio. Silencing Sirt3 abolished the beneficial effects of acacetin. Further analysis revealed that these effects of acacetin rely on Sirt1 activation by increasing NAD+ followed by increasing Sirt3, pAMPK and PGC-1α. In STZ-diabetic mice, acacetin significantly upregulated the decreased signaling molecules (i.e. SOD, Bcl-2, PGC-1α, pAMPK, Sirt3 and Sirt1) in aorta tissue and attenuated atherosclerosis. These results indicate that vascular endothelial protection of acacetin by activating Sirt1/Sirt3/AMPK signals is likely involved in alleviating diabetes-accelerated atherosclerosis by preserving mitochondrial function, which suggests that acacetin may be a drug candidate for treating cardiovascular disorder in patients with diabetes.

LncRNA LYPLAL1-DT in Type 2 Diabetes With Macrovascular Complication Contributes Protective Effects on Endothelial Cells via Regulating the miR-204-5p/SIRT1 Axis

“…It is one of the most important roles in vascular biology and atherogenesis [36]. For instance, SIRT1 can also protect endothelial cells from high glucose induced injury [34]. In the current study, we found SIRT1 is the target gene of LYPLAL1-DT, therefore elevates autophagy levels, thus decreasing apoptosis, in ammation, and monocyte adhesion of ECs.…”

“…In our study, novel lncRNA LYPLAL1-DT was found to regulate the target gene SIRT1 by acting as a ceRNA of miR-204-5p. SIRT1 is an anti-autophagy factor that can reduce cell death [34], as well as regulate the apoptosis of endothelial cells through the mTOR pathway [35]. It is one of the most important roles in vascular biology and atherogenesis [36].…”

Exosomes derived from pioglitazone-pretreated MSCs accelerate diabetic wound healing through enhancing angiogenesis

“…Prior studies have demonstrated that HG can induce endothelial cell apoptosis and dysfunction by activating NF-B signaling, leading to diabetic vascular complications [ 40 ]. Han et al reported that HG can suppress cell viability, induce cell apoptosis and cause oxidative stress injury in HUVECs, resulting in a vascular disorder in patients with diabetes [ 41 ]. In the present study, our results indicated that HG can inhibit HUVECs viability and proliferation, inducing cellular dysfunction and limiting migration, angiogenesis and wound healing.…”

Supplementation with a Cocoa–Carob Blend, Alone or in Combination with Metformin, Attenuates Diabetic Cardiomyopathy, Cardiac Oxidative Stress and Inflammation in Zucker Diabetic Rats

“…Accordingly, a very recent report described the protective effect of the flavone acacetin against cardiac senescence via SIRT1-mediated activation of SIRT6/AMPK signalling pathway [ 51 ]. Likewise, the protection of acacetin against vascular hyperglycemic injury was related to SIRT1-mediated activation of SIRT3/AMPK [ 52 ]. Moreover, SIRT6 and SIRT3 mutually regulate each other’s activity to protect the heart from developing diabetic cardiomyopathy [ 53 ].…”