Polyphenols and Polypeptides in Chinese Rice Wine Inhibit Homocysteine-induced Proliferation and Migration of Vascular Smooth Muscle Cells

Meng, Lingjun; Liu, Longbin; Zhou, Changzuan; Pan, Sunlei; Zhai, Xiaoya; Jiang, Chenyang; Guo, Yan; Zheng, Jing; Chi, Jufang; Peng, Fang; Guo, Hangyuan

doi:10.1097/fjc.0000000000000370

Cited by 23 publications

(27 citation statements)

References 31 publications

(34 reference statements)

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“…It has previously been demonstrated that elevated Hcy levels are a diagnosed cause of VSMC proliferation and further promote the formation of AS (21). The present study demonstrated that Hcy induced the proliferation of VSMCs, which may contribute to development of AS.…”

Section: Discussionsupporting

confidence: 69%

Homocysteine-induced proliferation of vascular smooth muscle cells occurs via PTEN hypermethylation and is mitigated by Resveratrol

Zhang

Jiao

et al. 2018

Mol Med Report

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Vascular smooth muscle cell (VSMC) proliferation is a primary pathological event in the development of atherosclerosis (AS), and the presence of homocysteine (Hcy) acts as an independent risk factor for AS. However, the underlying mechanisms remain to be elucidated. Phosphatase and tensin homologue on chromosome 10 (PTEN), is endogenously expressed in VSMCs and induces multiple signaling networks involved in cell proliferation, survival and inflammation, however, the specific role of PTEN is still unknown. The present study detected the proliferation ratio of VSMCs following treatment with Hcy and Resveratrol (RSV). In the 100 µM Hcy group, the proliferation ratio increased, and treatment with RSV decreased the proliferation ratio induced by Hcy. Reverse transcription‑quantitative polymerase chain reaction and western blotting were used to analyze PTEN expression, RSV treatment was associated with decreased PTEN expression levels in VSMCs. PTEN levels were decreased in Hcy treated cells, and the proliferation ratio of VSMCs were increased following treated with Hcy. To study the mechanism of regulation of PTEN by Hcy, the present study detected PTEN methylation levels in VSMCs, and PTEN DNA methylation levels were demonstrated to be increased in the 100 µM Hcy group, whereas treatment with RSV decreased the methylation status. DNA methyltransferase 1 is important role in the regulation of PTEN methylation. Overall, Hcy impacts the methylation status of PTEN, which is involved in cell proliferation, and induces the proliferation of VSMCs. This effect is alleviated by treatment with RSV, which exhibits an antagonistic mechanism against Hcy.

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Section: Discussionsupporting

confidence: 69%

Homocysteine-induced proliferation of vascular smooth muscle cells occurs via PTEN hypermethylation and is mitigated by Resveratrol

Zhang

Jiao

et al. 2018

Mol Med Report

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“…In the normal heart, the decomposition and synthesis of ECM are in dynamic equilibrium. The balance is maintained by MMPs and TIMPs (20). As TIMP-2 is an important member of the TIMP family, it can effectively inhibit the activity of MMP-2.…”

Section: Discussionmentioning

confidence: 99%

Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts

et al. 2018

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Cardiac fibrosis is a major pathological manifestation of diabetic cardiomyopathy (DCM), which leads to cardiac remodeling, dilated cardiomyopathy and congestive heart failure. Human cardiac fibroblasts (HCF) constitute the predominant cell type in the heart and matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are also involved in cardiac fibrosis. However, it is unclear whether high glucose levels affect the expression of MMPs and TIMPs in HCF. Sodium‑glucose cotransporter (SGLT) inhibitors have been developed as therapeutic agents and the anti‑DCM effect of SGLT inhibitors has been demonstrated by previous studies. However, whether SLGT inhibitors protect the diabetic heart by directly inhibiting the SGLTs in HCF in addition to lowering the blood glucose levels, has not yet been determined. In the present study, increased MMP‑2 expression was noted in HCFs in response to high glucose levels, which may be reversed by phlorizin (inhibits both SGLT1 and SGLT2), but not dapagliflozin (inhibits SGLT2). In addition, SGLT1 was revealed to be present in the HCFs and high glucose level was demonstrated to increase SGLT1 expression, which may be attenuated by phlorizin. Therefore it was concluded that high glucose levels induced MMP‑2 expression in the HCFs, potentially by upregulating SGLT1. SGLT1 inhibition may be a novel strategy for the treatment of DCM.

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“…It was worth noting that about 75% of hypertensive patients exhibit high homocysteine (Hcy) in China [ 6 ] and several studies have revealed that hyperhomocysteinemia interacts with hypertension in significantly increasing the risk of cardiovascular events (CVE) [ 7 ]. Elevated Hcy diminishes the vasodilation of nitric oxide, increases oxidative stress, stimulates the proliferation of vascular smooth muscle cells, lead to vascular constriction, and alters the elastic properties of the vascular wall [ 8 – 10 ]. In the last decades, researches have indicated a link between elevated Hcy and increased mortality among hypertensive patients [ 11 – 13 ].…”

Section: Introductionmentioning

confidence: 99%

Red cell distribution width and homocysteine act as independent risk factors for cardiovascular events in newly diagnostic essential hypertension

Gao²,

Wang

et al. 2017

Oncotarget

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Hyperhomocysteinemia and increased red cell distribution width (RDW) are associated with a higher possibility of adverse clinical outcomes of hypertension. The study aims to validate the effect of homocysteine (Hcy) and RDW on cardiovascular events (CVE) and investigate whether RDW is independently associated with serum Hcy in patients with essential hypertension (EH). The study reviewed 804 patients with newly diagnosed EH in our hospital. The clinical characteristics and laboratory results of all subjects were grouped according to the presence/absence of CVE. Patients in the CVE group had higher RDW and Hcy, as compared to the patients in the no CVE group. Multiple Cox regression analysis demonstrated that both RDW (HR = 1.24, 95% CI =1.02–1.56, P = 0.002) and Hcy (HR = 1.37, 95% CI = 1.02–1.80, P < 0.001) resulted significantly related to the CVE. Subsequent analysis found that patients with high RDW had higher Hcy levels as compared with those with low RDW (P = 0.007). Although Pearson's correlation suggested that RDW was positively correlated with Hcy (r = 0.122, P = 0.028), no significant correlation was observed between RDW and Hcy (β = 0.15, p = 0.126) after adjusted for a series of potential confounders using multiple linear regression analysis. In conclusion, RDW is not correlated with Hcy in patients with EH. Both RDW and Hcy are independent risk factors for CVE in newly diagnostic EH and have the potential to improve risk stratification.

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Polyphenols and Polypeptides in Chinese Rice Wine Inhibit Homocysteine-induced Proliferation and Migration of Vascular Smooth Muscle Cells

Cited by 23 publications

References 31 publications

Homocysteine-induced proliferation of vascular smooth muscle cells occurs via PTEN hypermethylation and is mitigated by Resveratrol

Homocysteine-induced proliferation of vascular smooth muscle cells occurs via PTEN hypermethylation and is mitigated by Resveratrol

Role of SGLT1 in high glucose level-induced MMP-2 expression in human cardiac fibroblasts

Red cell distribution width and homocysteine act as independent risk factors for cardiovascular events in newly diagnostic essential hypertension

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