Notoginsenoside Fc Accelerates Reendothelialization following Vascular Injury in Diabetic Rats by Promoting Endothelial Cell Autophagy

Abstract

Interventional therapies, such as percutaneous transluminal angioplasty and endovascular stent implantation, are used widely for the treatment of diabetic peripheral vascular complications. Reendothelialization is an essential process in vascular injury following interventional therapy, and hyperglycemia in diabetes mellitus (DM) plays an important role in damaging endothelial layer integrity, leading to the retardance of reendothelialization and excessive neointimal formation. Notoginsenoside Fc (Fc), a novel saponin isolated fromPanax notoginseng, effectively counteracts platelet aggregation. Nevertheless, the potential effects and molecular mechanisms of Fc on reendothelialization have yet to be explored. In this study, we present novel findings that show the benefit of Fc in accelerating reendothelialization and alleviating excessive neointimal formation following carotid artery injury in diabetic Sprague–Dawley ratsin vivo. Simultaneously, the decreased autophagy of the injured carotid artery in diabetic rats was restored by Fc treatment. Ourin vitroresults also demonstrated that Fc promoted endothelial cell proliferation and migration under high-glucose treatment by increasing autophagy. In summary, this study supported the notion that Fc could accelerate reendothelialization following vascular injury in diabetic rats by promoting autophagy, suggesting that Fc may exert therapeutic benefits for early endothelial injury and restenosis following intervention in diabetes-associated vascular diseases.

<p>miR145 Regulates the Proliferation and Apoptosis of Rat Vascular Endothelial Cells under Hyperglycemia by Targeting the <em>ANGPT2</em> Gene and Involving the NFκB Signaling Pathway</p>

“…1 There are >300 million individuals suffering from DM worldwide, and approximately 60%-80% of DM patients present with vascular complications. 2 Diabetic vascular complications are characterized by endothelial cell dysfunction and the formation of atherosclerotic plaques, due to micro-and macrovascular lesions. 3 DM and its complications have become epidemic, and pose a serious challenge to worldwide health-care systems.…”

Physiological and pathological characteristics of vascular endothelial injury in diabetes and the regulatory mechanism of autophagy

“…Several studies have proved that DM patients have impaired autophagy in the vascular endothelium compared with non-DM patients and that impaired autophagy induces and aggravates vascular endothelium morphological abnormalities and dysfunction, including EC apoptosis and exfoliation ( 72 , 73 ), EG reduction ( 72 ), insufficient EC migration and generation ( 10 ), increased oxidative stress ( 74 , 75 ), and blocked eNOS activation ( 76 ). The recovery of damaged autophagy can prevent vascular endothelial injury in DM ( 10 , 76 ). Therefore, autophagy regulation is expected to become an important strategy for delaying and improving DM angiopathy.…”

“…DM is a complex disease that is accompanied by glucose and lipid metabolism disorders, IR, inflammatory reaction initiation, and oxidative stress activation. Activating autophagy in aortic endothelial cells (ECs) can reduce vascular inflammation and atherosclerosis onset ( 9 ) and accelerate endothelial regeneration after injury in DM rats ( 10 ), indicating that autophagy regulates vascular endothelium to participate in the progression of vascular lesions in DM. Contrastingly, another mechanism to improve hyperglycemia-induced endothelial injury is achieved by downregulating autophagy ( 11 ).…”

Notoginsenoside Fc ameliorates renal tubular injury and mitochondrial damage in acetaminophen-induced acute kidney injury partly by regulating SIRT3/SOD2 pathway

“…Fc has been demonstrated to produce many pharmacological effects ( 11 , 12 ). One recent report demonstrated Fc accelerated re-endothelialization following vascular injury in diabetic rats through promoting autophagy ( 13 ). Fc could ameliorate vascular endothelial cell injury by regulation of PPAR-γ-mediated pathway in diabetic rats ( 14 ).…”