The apolipoprotein A-I mimetic peptide, D-4F, alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway

Liu, Donghui; Ding, Zhenzhen; Wu, Mengzhang; Xu, Wenqi; Qian, Mingming; Du, Qian; Zhang, Le; Cui, Ye; Zheng, Jinbao; Chang, He; Huang, Caihua; Lin, Donghai; Wang, Yan

doi:10.1016/j.yjmcc.2017.01.017

Cited by 34 publications

(33 citation statements)

References 45 publications

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“…HUVECs are accepted and widely used in vitro investigations for endothelial disorders of arteries [61] , [62] , [63] , [64] . Although HUVECs exhibit phenotypic and functional differences versus human arterial endothelial cells (HAECs) [65] , considering the limited lifespan and the unstable characteristics of the primary HAECs [66] , we adopted the immortalized HUVEC cell line [64] in our study that are generally better characterized and more stable in their endothelial traits [66] .…”

Section: Discussionmentioning

confidence: 99%

Blocking mitochondrial cyclophilin D ameliorates TSH-impaired defensive barrier of artery

Liu

Chai

et al. 2018

Redox Biology

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AimsEndothelial cells (ECs) constitute the defensive barrier of vasculature, which maintains the vascular homeostasis. Mitochondrial oxidative stress (mitoOS) in ECs significantly affects the initiation and progression of vascular diseases. The higher serum thyroid stimulating hormone (TSH) level is being recognized as a nonconventional risk factor responsible for the increased risk of cardiovascular diseases in subclinical hypothyroidism (SCH). However, effects and underlying mechanisms of elevated TSH on ECs are still ambiguous. We sought to investigate whether cyclophilin D (CypD), emerging as a crucial mediator in mitoOS, regulates effects of TSH on ECs.Methods and resultsSCH patients with TSH > = 10 mIU/L showed a positive correlation between serum TSH and endothelin-1 levels. When TSH levels declined to normal in these subjects after levothyroxine therapy, serum endothelin-1 levels were significantly reduced. Supplemented with exogenous thyroxine to keep normal thyroid hormones, thyroid-specific TSH receptor (TSHR)-knockout mice with injection of exogenous TSH exhibited elevated serum TSH levels, significant endothelial oxidative injuries and disturbed endothelium-dependent vasodilation. However, Tshr-/- mice resisted to TSH-impaired vasotonia. We further confirmed that elevated TSH triggered excessive mitochondrial permeability transition pore (mPTP) opening and mitochondrial oxidative damages in mouse aorta, as well as in cultured ECs. Genetic or pharmacological inhibition of CypD (the key regulator for mPTP opening) attenuated TSH-induced mitochondrial oxidative damages and further rescued endothelial functions. Finally, we confirmed that elevated TSH could activate CypD by enhancing CypD acetylation via inhibiting adenosine monophosphate-activated protein kinase/sirtuin-3 signaling pathway in ECs.ConclusionsThese findings reveal that elevated TSH triggers mitochondrial perturbations in ECs and provide insights that blocking mitochondrial CypD enhances the defensive ability of ECs under TSH exposure.

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Section: Discussionmentioning

confidence: 99%

Blocking mitochondrial cyclophilin D ameliorates TSH-impaired defensive barrier of artery

Liu

Chai

et al. 2018

Redox Biology

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“…D-4F protects endothelial cells against ox-LDL-induced injury by antagonizing the downregulation of pigment epithelium-derived factor (PEDF) [105]. We also found that D-4F alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway [165]. Besides, D-4F accelerates vasodilatation and restrains atherosclerosis by regulating phospholipid metabolites and decreasing plasma LysoPC in LDL-R null mice [166].…”

Section: Apoa-i Mimetic Peptidesmentioning

confidence: 99%

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

Liu¹

2020

Apolipoproteins, Triglycerides and Cholesterol

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High-density lipoprotein (HDL) is a heterogeneous particle composed of apolipoproteins, enzymes, and lipids. Besides transporting cholesterol to the liver, HDL also exerts many protections on anti-oxidation, anti-inflammation, and anti-apoptosis. Initial understandings of HDL came from its protective roles against atherosclerosis and the observation that high plasma HDL cholesterol (HDL-C) levels seemed to decrease cardiovascular disease (CVD) attack. However, those patients either with cholesterol ester transfer protein (CETP) deficiency or taking CETP inhibitors substantially elevated HDL-C levels but did not necessarily decrease CVD risk. Thus, some researchers suggested that quantitative measurements of HDL particle (HDL-P) might be more valuable than traditional HDL-C measurements. What is more bewildering is that HDL from patients with systemic inflammation decreased its protective effects and even became a pro-inflammatory factor. Recently, synthesized HDL and apolipoprotein mimetic peptides showed biological functions similar to native ones. Expectedly, lots of novel measurement methods and therapeutic agents about HDL would be established soon.

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“…Moreover, the antioxidation, proproliferation, and promigration abilities of apoA-I were cut down by the inhibitors of both eNOS and HO-1. [ 25 ] Next, increasing high-density lipoprotein (HDL) concentrations by inhibiting the cholesteryl ester transfer protein reduces intimal thickening and regenerates functional endothelia in damaged aortas in a scavenger receptor-B1-dependent and phosphatidylinositol-4,5-bisphosphate 3-kinase/Akt-dependent manner. [ 26 ] In summary, the results suggest that apoA-I and cholesteryl ester transfer protein inhibition might be commendable candidates for the protection of ECs and the prevention of atherosclerotic disease.…”

Section: P Rotective F Actors Rmentioning

confidence: 99%

Common Injuries and Repair Mechanisms in the Endothelial Lining

Meng

Chen

Zhang

et al. 2018

Chinese Medical Journal

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Objective:Endothelial cells (ECs) are important metabolic and endocrinal organs which play a significant role in regulating vascular function. Vascular ECs, located between the blood and vascular tissues, can not only complete the metabolism of blood and interstitial fluid but also synthesize and secrete a variety of biologically active substances to maintain vascular tension and keep a normal flow of blood and long-term patency. Therefore, this article presents a systematic review of common injuries and healing mechanisms for the vascular endothelium.Data Sources:An extensive search in the PubMed database was undertaken, focusing on research published after 2003 with keywords including endothelium, vascular, wounds and injuries, and wound healing.Study Selection:Several types of articles, including original studies and literature reviews, were identified and reviewed to summarize common injury and repair processes of the endothelial lining.Results:Endothelial injury is closely related to the development of multiple cardiovascular and cerebrovascular diseases. However, the mechanism of vascular endothelial injury is not fully understood. Numerous studies have shown that the mechanisms of EC injury mainly involve inflammatory reactions, physical stimulation, chemical poisons, concurrency of related diseases, and molecular changes. Endothelial progenitor cells play an important role during the process of endothelial repair after such injuries. What's more, a variety of restorative cells, changes in cytokines and molecules, chemical drugs, certain RNAs, regulation of blood pressure, and physical fitness training protect the endothelial lining by reducing the inducing factors, inhibiting inflammation and oxidative stress reactions, and delaying endothelial caducity.Conclusions:ECs are always in the process of being damaged. Several therapeutic targets and drugs were seeked to protect the endothelium and promote repair.

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The apolipoprotein A-I mimetic peptide, D-4F, alleviates ox-LDL-induced oxidative stress and promotes endothelial repair through the eNOS/HO-1 pathway

Cited by 34 publications

References 45 publications

Blocking mitochondrial cyclophilin D ameliorates TSH-impaired defensive barrier of artery

Blocking mitochondrial cyclophilin D ameliorates TSH-impaired defensive barrier of artery

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

Common Injuries and Repair Mechanisms in the Endothelial Lining

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