Abstract
Background and AimsEndothelial senescence is an important risk factor leading to atherosclerosis. The mechanism of quercetin against endothelial senescence is worth exploring.MethodsQuercetin (20 mg/kg/d) was administered to ApoE-/- mice intragastrically to evaluate the effectiveness of quercetin on atherosclerotic lesion in vivo. In vitro, human aortic endothelial cells (HAECs) were used to assess the effect of quercetin on cellular senescence induced by oxidized low-density lipoprotein (ox-LDL). Transcriptome microarray and quantitative RT-PCR was conducted to study the pharmacological targets of quercetin.ResultsApoE-/- mice demonstrated obvious lipid deposition in arterial lumina, high level of serum sIcam-1 and IL-6, and high density of Vcam-1 and lower density of Sirt1 in aorta. Quercetin administration decreased lipid deposition in arterial lumina, serum sIcam-1, and IL-6 and Vcam-1 in aorta, while increased the density of Sirt1 in aorta of ApoE-/- mice. In vitro, quercetin (0.3, 1, or 3 μmol/L) decreased the expression of senescence-associated β-galactosidase and improved cell morphology of HAECs. And quercetin decreased the cellular apoptosis and increased mitochondrial membrane potential (ΔΨm) in dose-dependent manner, and decreased ROS generation simultaneously. Transcriptome microarray suggested 254 differentially expressed (DE) mRNAs (110 mRNAs were upregulated and 144 mRNAs were downregulated) in HAECs after quercetin treatment (fold change > 1.5, P < 0 .05, Que vs Ox-LDL). GO and KEGG analysis indicated nitrogen metabolism, ECM-receptor interaction, complement, and coagulation cascades, p53 and mTOR signaling pathway were involved in the pharmacological mechanisms of quercetin against ox-LDL.ConclusionsQuercetin alleviated atherosclerotic lesion both in vivo and in vitro.
Highlights
Aging is an independent cardiovascular risk factor associated to endothelial dysfunction and arterial stiffness, which is a considered as very early event leading to cardiovascular disease (El Assar et al, 2012)
Quercetin significantly decreased the level of serum soluble intercellular adhesion molecule-1 (sIcam-1) and IL-6 in ApoE-/- mice (P < 0.05, Figures 1C, D)
The photograph and semi-quantitative analysis of Immunohistochemical Staining (IHC) sugggested that ApoE-/- mice had higher density of vascular cell adhesion molecule-1 (Vcam-1) and lower density of sirtuin 1 (Sirt1) in aorta than that of C57, while quercetin decreased the density of Vcam-1 and increased the density of Sirt1 effectively (P < 0.05, Figure 1E)
Summary
Aging is an independent cardiovascular risk factor associated to endothelial dysfunction and arterial stiffness, which is a considered as very early event leading to cardiovascular disease (El Assar et al, 2012). The mitochondrial DNA (MtDNA) is susceptible to damage partly owing to the absence of protective histones within the DNA duplex, and as a result of the close proximity to the ROS-producing inner mitochondrial membrane Both nuclear and mitochondrial DNA damage, defects in protein processing, intercellular communication dysfunction, and senescence -associated secretory phenotype are involved in cellular senescence (Ló pez-Otın et al, 2013; Uryga and Bennett, 2016). Human aortic endothelial cells (HAECs) were used to assess the effect of quercetin on cellular senescence induced by oxidized low-density lipoprotein (ox-LDL). Quercetin administration decreased lipid deposition in arterial lumina, serum sIcam-1, and IL-6 and Vcam-1 in aorta, while increased the density of Sirt in aorta of ApoE-/- mice. GO and KEGG analysis indicated nitrogen metabolism, ECM-receptor interaction, complement, and coagulation cascades, p53 and mTOR signaling pathway were involved in the pharmacological mechanisms of quercetin against ox-LDL
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
