Folate Reverses NF-κB p65/Rela/IL-6 Level Induced by Hyperhomocysteinemia in Spontaneously Hypertensive Rats

Zhang, Lihua; Li, Zhongliang; Xing, Changcheng; Gao, Ning; Xu, Rui

doi:10.3389/fphar.2021.651582

Cited by 9 publications

(7 citation statements)

References 44 publications

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“…Studies found that HHcy can significantly increase cardiovascular and cerebrovascular events in hypertension 5 . Another study found that the levels of oxidative stress and inflammation are increased in hypertension associated with HHcy 6 . However, the molecular mechanism of HHcy synergistically aggravating the arterial damage in hypertension is rarely reported.…”

Section: Introductionmentioning

confidence: 97%

“…study demonstrated that Nox is involved in the target organ damage of hypertension and HHcy-induced oxidative stress 6 . However, it is unclear whether oxidative stress is the leading cause for arterial pathological changes of hypertension associated with HHcy, and whether HHcy aggravates the arterial damage of hypertension through Nox2 or Nox4 signaling pathways.…”

mentioning

confidence: 93%

“…Nox is an important molecule of the integrated stress response in the body and can produce reactive oxygen species (ROS) that leads to malondialdehyde (MDA) and inhibits superoxide dismutase (SOD). Previous study demonstrated that Nox is involved in the target organ damage of hypertension and HHcy-induced oxidative stress 6 . However, it is unclear whether oxidative stress is the leading cause for arterial pathological changes of hypertension associated with HHcy, and whether HHcy aggravates the arterial damage of hypertension through Nox2 or Nox4 signaling pathways.…”

Section: Introductionmentioning

confidence: 99%

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Mechanism of arterial injury exacerbated by hyperhomocysteinemia in spontaneously hypertensive rats

Zhang

et al. 2023

Sci Rep

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Hypertension associated with hyperhomocysteinemia (HHcy) accounts for 75% of hypertension in China. HHcy plays a synergistic role with hypertension in vascular injury and significantly increases the incidence of cardiovascular and cerebrovascular diseases. The present study aimed to explore the molecular mechanism of HHcy-induced arterial injury in hypertension. Spontaneously hypertensive rats (SHR) were injected intraperitoneally with DL-homocysteine (Hcy) to construct the model of hypertension associated with HHcy (HHcy + SHR). Biological network was employed to identify the material basis of arterial injury in hypertension associated with HHcy. The prediction molecules in oxidative stress and inflammation pathways were experimentally verified by quantitative real-time polymerase chain reaction (qRT-PCR) and western blot (WB) analysis. The HHcy + SHR group significantly increased oxidative stress pathway molecules: nicotinamide adenine dinucleotide phosphate oxidase (Nox); inflammatory pathway molecules: vascular adhesion protein-1 (VAP-1), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-a); as well as inflammatory pathway regulatory factors: nuclear factor-κ-gene binding (NF-κB) p65 and protein kinase B (Akt1). Among them, IL-6 was also significantly increased in the HHcy group. Both oxidative stress and inflammation contributed to the arterial injury of hypertension associated with HHcy, and inflammation mechanism might play a leading role in HHcy aggravating arterial injury, at least partially through the Akt1/NF-κB p65/IL-6 signaling pathway.

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Section: Introductionmentioning

confidence: 97%

mentioning

confidence: 93%

Section: Introductionmentioning

confidence: 99%

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Mechanism of arterial injury exacerbated by hyperhomocysteinemia in spontaneously hypertensive rats

Zhang

et al. 2023

Sci Rep

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“…Plasma Hcy levels of 10 or more μmol/L were considered to indicate H-type hypertension in China’s “H-type hypertension diagnosis and therapy of expert consensus” in 2016. HHcy up-regulates the expression of interleukin-6 (IL-6) and nuclear factor-κB (NF-κB) p65/Rela, induces oxidative stress and inflammation, and leads to hypertension [ 15 ]. Boachie et al found that low vitamin B12 levels can increase metabolic disorders and induce hypertension by affecting epigenetic mechanisms, such as DNA methylation, histone modifications and micro-RNA [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

Untargeted Metabolomics Analysis Using UHPLC-Q-TOF/MS Reveals Metabolic Changes Associated with Hypertension in Children

Zhang

Liu

et al. 2023

Nutrients

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The mechanism of hypertension in children remains elusive. The objective of this study was to analyze plasma metabolomics characteristics to explore the potential mechanism of hypertension in children. Serum samples from 29 control children, 38 children with normal body mass index and simple hypertension (NBp), 8 children overweight with simple hypertension (OBp), 37 children with normal body mass index and H-type hypertension (NH) and 19 children overweight with H-type hypertension (OH) were analyzed by non-targeted metabolomics. A total of 1235 differential metabolites were identified between children with hypertension and normal controls, of which 193 metabolites including various lipids were significantly expressed. Compared with the control group, 3-dehydroepiandrosterone sulfate, oleic acid and linoleic acid were up-regulated, and gamma-muricholic acid was down-regulated in the NBp group; 3-dehydroepiandrosterone sulfate, 4-acetamidobutanoate and 1-hexadecanoyl-2-octadecadienoyl-sn-glyero-3-phosphocholine were up-regulated in the OBp group, whereas adenosine and 1-myristoyl-sn-glyero-3-phosphocholine were down-regulated; in the NH group, 1-palmitoyl-2-linoleoyl-sn-glycero-3-phosphocholine, phenol and 3-methoxytyramine were up-regulated, while pentadecanoic acid was down-regulated; in the OH group, NG,NG-dimethyl-L-arginine, 1-palmitoyl-sn-glycero-3-phosphocholine and monoethyl phthalate were up-regulated, while phloretin and glycine were down-regulated. The results showed that the children with hypertension had obvious disorders of lipid metabolism (especially in the overweight hypertension group), which led to the occurrence of hypertension. Additionally, the concentration of NO production-related NG, NG-dimethyl-L-arginine, was significantly increased, which may play an important role in H-type hypertension in children.

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“…4 It is well known that folic acid (FA) can alleviate HHcy. 5 Folic acid is one of the essential vitamins of the human body, and participates in the coenzyme of many human enzymes. 6 Folic acid is also an important antioxidant in the body.…”

Section: Introductionmentioning

confidence: 99%

Comparison of the antihypertensive effects of folic acid and resveratrol in spontaneously hypertensive rats combined with hyperhomocysteinemia

Lu,

Zhang,

Wang

et al. 2023

SAGE Open Medicine

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Objectives: Studies have found that both folic acid and resveratrol have potential benefits in reducing complications of hypertension. The aim of this study was to compare the effects of resveratrol and folic acid on blood pressure in spontaneously hypertensive rats combined with hyperhomocystinemia, and to explore their potential mechanisms. Methods: Twenty-four male specific pathogen free (SPF) SPF grade spontaneously hypertensive rats were randomly divided into four groups: the SHR group, the hypertension combined with hyperhomocystinemia group (SHR + HHcy), the folic acid intervention group (SHR + HHcy + FA), and the resveratrol intervention group (SHR + HHcy + Res). The rat model of hypertension combined with hyperhomocystinemia was constructed, and then folic acid or resveratrol were given by gavage. Rat tail artery blood pressure, serum homocysteine concentration, superoxide dismutase activity, malondialdehyde levels, and mRNA transcription and protein expression of endothelial nitric oxide synthase and angiotensin II were detected. Result: Compared with the SHR group, the SHR + HHcy group significantly increased hyperhomocystinemia and malondialdehyde levels, and inhibited superoxide dismutase activity and endothelial nitric oxide synthase expression. Compared with the SHR + HHcy group, the SHR + HHcy + FA group significantly reduced hyperhomocystinemia and malondialdehyde levels, and significantly increased superoxide dismutase activity and endothelial nitric oxide synthase expression; the SHR + HHcy + Res group also inhibited malondialdehyde levels and promoted endothelial nitric oxide synthase expression, but did not reduce hyperhomocystinemia. When comparing between the SHR + HHcy + FA group and the SHR + HHcy + Res group, folic acid significantly decreased hyperhomocystinemia and increased superoxide dismutase activity, while resveratrol significantly decreased blood pressure and angiotensin II expression. Conclusions: Both resveratrol and folic acid reduced the levels of oxidative stress and promoted the expression of endothelial nitric oxide synthase in SHRs combined with hyperhomocystinemia. Moreover, resveratrol exhibited superior antihypertensive efficacy compared to folic acid, potentially attributed to its ability to inhibit angiotensin II expression.

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Folate Reverses NF-κB p65/Rela/IL-6 Level Induced by Hyperhomocysteinemia in Spontaneously Hypertensive Rats

Cited by 9 publications

References 44 publications

Mechanism of arterial injury exacerbated by hyperhomocysteinemia in spontaneously hypertensive rats

Mechanism of arterial injury exacerbated by hyperhomocysteinemia in spontaneously hypertensive rats

Untargeted Metabolomics Analysis Using UHPLC-Q-TOF/MS Reveals Metabolic Changes Associated with Hypertension in Children

Comparison of the antihypertensive effects of folic acid and resveratrol in spontaneously hypertensive rats combined with hyperhomocysteinemia

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