Role of Hyperhomocysteinemia and Hyperuricemia in Pathogenesis of Atherosclerosis

Zhao, Junjie; Chen, Hailin; Liu, Ning; Chen, Jun; Gu, Yibin; Chen, Jiangjun; Yang, Kui

doi:10.1016/j.jstrokecerebrovasdis.2016.10.012

Cited by 68 publications

(46 citation statements)

References 33 publications

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“…In this study, the level serum XO increased significantly in the rats administered only NaF. It can be extrapolated that the increase in serum level of XO was an indication of hyperuricemia which is major pointer to oxidative stress, inflammation, renal damage and hypertension, arteriosclerosis, and myocardial infarction . The ability of Luteolin to inhibit the activities of MPO and XO confirms the antioxidant, anti‐inflammatory, cardioprotective and reno‐protective effect of Luteolin .…”

Section: Discussionsupporting

confidence: 68%

Luteolin‐mediated Kim‐1/NF‐kB/Nrf2 signaling pathways protects sodium fluoride‐induced hypertension and cardiovascular complications

et al. 2018

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The use of sodium fluoride (NaF) as a major ingredient for tooth paste, mouth wash, and mouth rinse has become inevitable in our day-to-day life. However, flavonoids such as Luteolin might be of great value in the prevention of toxicity associated with accidental or inevitable ingestion of NaF. In the study, 40 male Wistar albino rats were randomly divided into four groups with 10 rats in a group. Group A was the control group and received normal saline, Group B was exposed to NaF at 300 ppm (300 mg/L) in drinking water daily for a week, Groups C and D were exposed to 300 ppm (300 mg/L) of NaF and coadministered with Luteolin orally daily at a dosage of 100 mg/kg and 200 mg/kg for the same time point. Our results indicated that NaF caused significant increases in systolic blood pressure, diastolic blood pressure, mean arterial pressure, malondialdehyde, protein carbonyl, myeloperoxidase, advanced oxidative protein products, together with significant reductions in glutathione peroxidase, superoxide dismutase, catalase, glutathione reductase, reduced glutathione, and nitric oxide (NO) bioavailability. The electrocardiogram results showed that NaF alone caused significant prolongation of QT and QTc intervals. Immunohistochemistry revealed that NaF caused increase expressions of Kidney injury marker 1 (Kim-1), nuclear factor 518 BioFactors Research Communication kappa bet (NF-κB), nuclear factor erythroid 2-related factors 2 (Nrf2), and cardiac troponin I (CTnI). Together, Luteolin coadministration with NaF improved NO bioavailability, reduced high blood pressure, markers of oxidative stress, reversed prolongation of QT and QTc intervals, and lowered the expressions of Kim-1, NF-κB, and CTnI. © 2018 BioFactors, 44(6):518-531, 2018

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Section: Discussionsupporting

confidence: 68%

Luteolin‐mediated Kim‐1/NF‐kB/Nrf2 signaling pathways protects sodium fluoride‐induced hypertension and cardiovascular complications

et al. 2018

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“…Atherosclerosis results from multiple processes, including endothelial dysfunction, vascular smooth muscle cell proliferation, inflammation, oxidative stress, and matrix alteration. Among these, endothelial dysfunction is pivotal in the initiation and development of atherosclerosis [1, 2]. Homocysteine (Hcy)is an independent risk factor for atherosclerosis, and is thought to contribute to endothelial dysfunction through Hcy-induced cell injury [3].…”

Section: Introductionmentioning

confidence: 99%

Oxymatrine Inhibits Homocysteine-Mediated Autophagy via MIF/mTOR Signaling in Human Umbilical Vein Endothelial Cells

Zhang

Zhang²,

Tang

et al. 2018

Cell Physiol Biochem

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Background/Aims: Genetic or nutritional deficiencies in homocysteine (Hcy)metabolism lead to the accumulation of Hcy and its metabolites in the blood. This can lead to hyperhomocysteinemia (HHcy), which is an independent risk factor for cardiovascular disease. Studies have shown that HHcy leads to endothelial dysfunction, a hallmark of atherosclerosis, which may explain this link. The precise mechanism remains unclear, but a strong possibility is excessive HHCy-induced autophagy. Autophagy has been better studied in ischemia/reperfusion (I/R) injuries, and previous work showed that Oxymatrine (OMT), a quinolizidine alkaloid, protects cells against myocardial I/R injury by inhibiting autophagy. The aim of this study was to determine whether OMT inhibits autophagy in HHcy. Methods: Autophagy in HUVEC cells treated with Hcy in the presence and absence of OMT was visualized bytransmission electron microscopy and the degree was determined by western blotting and qRT-PCR. Small interfering RNA (siRNA)was used to determine the efficiency of Macrophage migration inhibitory factor (MIF) inhibition. Cell apoptosis wasdetected by western blotting and flow cytometric analysis. Results: OMT inhibited autophagy, MIF, and mTOR in HUVECs during Hcy exposure, depending on the dose. siRNA-mediated MIF knockdown decreased Hcy-induced autophagy, while administration of 3-methyladenosine and rapamycin showed that they also induce autophagy. Furthermore, OMT dose-dependently inhibited the Hcy-induced HUVEC apoptosis/death. Conclusions: These results suggest that Hcy can evokeautophagy-activated HUVEC apoptosis/death via a MIF/mTOR signaling pathway, which can be reversed by OMT. Our results provide a new insight into a functional role of OMT in the prevention of Hcy-induced HUVEC injury and death.

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“…Homocysteine (Hcy) is derived from sulfur‐containing and non‐proteinogenic amino acid, and during the metabolism of methionine, it is formed in trace amount. Hyperhomocysteinemia (HHcy) can induces vascular endothelial injury, and has been determined to be one of the main risk factors for cardiovascular diseases, but its exact mechanism remains unclear . Lectin‐like oxLDL receptor‐1 (LOX‐1) is an essential receptor for oxide low‐density lipoprotein (oxLDL), and plays a vital role in atherosclerotic process .…”

Section: Introductionmentioning

confidence: 99%

Picroside II attenuates hyperhomocysteinemia‐induced endothelial injury by reducing inflammation, oxidative stress and cell apoptosis

Wang

Hong

Zhang

et al. 2018

J Cellular Molecular Medi

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Picroside II (P‐II), one of the main active components of scrophularia extract, which have anti‐oxidative, anti‐inflammatory effects, but its effect on hyperhomocysteinemia (HHcy) induced endothelial injury remains to be determined. Here, we test whether P‐II protects HHcy‐induced endothelial dysfunction against oxidative stress, inflammation and cell apoptosis. In vitro study using HUVECs, and in hyperhomocysteinemia mouse models, we found that HHcy decreased endothelial SIRT1 expression and increased LOX‐1 expression, subsequently causing reactive oxygen species generation, up‐regulation of NADPH oxidase activity and NF‐κB activation, thereby promoting pro‐inflammatory response and cell apoptosis. Blockade of Sirt1 with Ex527 or siRNASIRT1 increased LOX‐1 expression, whereas overexpression of SIRT1 decreased LOX‐1 expression markedly. P‐II treatment significantly increased SIRT1 expression and reduced LOX‐1 expression, and protected against endothelial cells from Hcy‐induced oxidative injury, inflammation and apoptosis. However, blockade of SIRT1 or overexpression of LOX‐1 attenuated the therapeutic effects of P‐II. In conclusion, our results suggest that P‐II prevents the Hcy induced endothelial damage probably through regulating the SIRT1/LOX‐1 signaling pathway.

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Role of Hyperhomocysteinemia and Hyperuricemia in Pathogenesis of Atherosclerosis

Cited by 68 publications

References 33 publications

Luteolin‐mediated Kim‐1/NF‐kB/Nrf2 signaling pathways protects sodium fluoride‐induced hypertension and cardiovascular complications

Luteolin‐mediated Kim‐1/NF‐kB/Nrf2 signaling pathways protects sodium fluoride‐induced hypertension and cardiovascular complications

Oxymatrine Inhibits Homocysteine-Mediated Autophagy via MIF/mTOR Signaling in Human Umbilical Vein Endothelial Cells

Picroside II attenuates hyperhomocysteinemia‐induced endothelial injury by reducing inflammation, oxidative stress and cell apoptosis

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