Salidroside inhibits high-glucose induced proliferation of vascular smooth muscle cells via inhibiting mitochondrial fission and oxidative stress

Abstract

The mitochondria are highly dynamic organelles, carefully maintaining network homeostasis by regulating mitochondrial fusion and fission. Mitochondrial dynamics are involved in the regulation of a variety of pathophysiological processes, including cell proliferation. Oxidative stress serves an important role in the remodeling of arterial vascular tissue in diabetic patients by affecting the proliferation of vascular smooth muscle cells (VSMCs). Salidroside is the primary active component of Rhodiola rosea and has been demonstrated to be an antioxidant with cardio- and vascular-protective effects, in addition to improving glucose metabolism. Therefore, the present study aimed to examine the impact of Salidroside on VSMC proliferation, reactive oxygen species (ROS) generation and mitochondrial dynamics under high glucose conditions and the potential mechanisms involved. The current study used Salidroside and a mitochondrial division inhibitor, specifically of Drp1 (Mdivi-1) to treat VSMCs under high glucose conditions for 24 h and assessed VSMCs proliferation, the state of mitochondrial fission and fusion and the expression level of proteins related to mitochondrial dynamics including dynamin-related protein (Drp1) and mitofusin 2 (Mfn2), ROS level and nicotinamide adenine dinucleotide phosphate oxidase activity. The results of the present study indicate that Salidroside and Mdivi-1 inhibit VSMC proliferation, Drp1 expression and oxidative stress and upregulate Mfn2 expression (all P<0.05). The inhibitive effect on VSMC proliferation may be partly reversed by exogenous ROS. In addition, the inhibitive effect on VSMCs proliferation and oxidative stress may also be in part reversed by Mfn2-siRNA. Collectively, these data suggest that Salidroside inhibits VSMCs proliferation induced by high-glucose and may perform its therapeutic effect via maintaining mitochondrial dynamic homeostasis and regulating oxidative stress level, with Mfn2 as a therapeutic target.