miR‐195‐3p alleviates homocysteine‐mediated atherosclerosis by targeting IL‐31 through its epigenetics modifications

Xiong, Jiantuan; Ma, Fang; Ding, Ning; Xu, Lingbo; Ma, Shengchao; Ai, Yang; Hao, Yinju; Zhang, Huiping; Jiang, Yideng

doi:10.1111/acel.13485

Cited by 23 publications

(11 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, advances have shown that increased Hcy in serum level is a primary cause of cardiovascular diseases, diabetes, neurodegenerative diseases, and so on. Hcy was also involved in the initiation and progression of atherosclerosis by inhibiting the expression of miR-195-3p and in turn, enhancing the inflammation through IL-31 ( 21 ). In cardiovascular diseases, Hcy was reported to cause endothelial dysfunction through ENaC, or the toxicity related to iron containing proteins.…”

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia Is a Predictor for Poor Postoperative Angiogenesis in Adult Patients With Moyamoya Disease

et al. 2022

Front. Neurol.

View full text Add to dashboard Cite

Background and PurposesThe risk factors of poor postoperative angiogenesis in moyamoya disease (MMD) patients remain unknown. We aimed to investigate the association between hyperhomocysteinemia (HHcy) and postoperative angiogenesis of adult patients with MMD.MethodsA total of 138 adult patients with MMD were prospectively recruited from July 1 to December 31, 2019. After excluding 10 patients accepting conservative therapy and 77 individuals without postoperative digital subtraction angiography (DSA), all 51 MMD patients were enrolled, and 28 patients received bilateral operations separately. Patients were grouped according to postoperative angiogenesis and HHcy presentation, respectively. Clinical data and laboratory examinations were compared. Potential risk factors were evaluated by univariate and multivariate logistic regression analysis. Nomogram was further performed. The biological functions of homocysteine (Hcy) were explored in vitro.ResultsComparing to the normal, patients with poor postoperative angiogenesis were higher in serum Hcy (p = 0.004), HHcy ratio (p = 0.011), creatinine (Cr) (p < 0.001), uric acid (UA) (p = 0.036), Triglyceride (p = 0.001), high-density lipoprotein cholesterol (HDL-C) (p = 0.001), low-density lipoprotein cholesterol (LDL-C) (p = 0.009), ApoA (p = 0.022), apolipoprotein B (ApoB) (p = 0.013). Furthermore, HHcy was more common in men (p = 0.003) than women. Logistic analysis results showed that Hcy (OR = 0.817, 95% CI = 0.707–0.944, p = 0.006) was an independent risk factor. HHcy and Cr were significantly associated with poor postoperative angiogenesis in MMD patients. Further, Hcy could inhibit the proliferation, migration, and tube formation of human brain microvascular endothelial cells (HBMECs), which can be reversed by vascular endothelial growth factor (VEGF).ConclusionThe HHcy was significantly correlated with poor postoperative angiogenesis in adult patients with MMD. Hcy significantly inhibits HBMECs proliferation, migration, and tube formation. Furthermore, VEGF could reverse the inhibition effect induced by Hcy. Lowering the level of Hcy may be beneficial for postoperative MMD patients. Focusing on the pathophysiology and mechanism of HHcy might help to guide postoperative clinical management.

show abstract

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia Is a Predictor for Poor Postoperative Angiogenesis in Adult Patients With Moyamoya Disease

et al. 2022

Front. Neurol.

View full text Add to dashboard Cite

show abstract

“…It is widely accepted that chronic progressive inflammation has deleterious and additive effects that accelerate AS and contribute to lesion rupture [ 31 ]. HHcy promotes pro-inflammatory cytokine production and lipid accumulation in macrophages and has been regarded as a major driving force in the development of atherosclerotic plaques.…”

Section: Discussionmentioning

confidence: 99%

HHcy Induces Pyroptosis and Atherosclerosis via the Lipid Raft-Mediated NOX-ROS-NLRP3 Inflammasome Pathway in apoE−/− Mice

Liu

Teishima

Fu-jian

et al. 2022

Cells

View full text Add to dashboard Cite

Lipid rafts play important roles in signal transduction, particularly in responses to inflammatory processes. The current study aimed to identify whether lipid raft-mediated inflammation contributes to hyperhomocysteinemia (HHcy)-accelerated atherosclerosis (AS), and to investigate the underlying mechanisms. THP-1-derived macrophages were used for in vitro experiments. ApoE−/− mice were fed a high-fat diet for 12 weeks to establish an AS model, and a high-fat plus high-methionine diet was used to induce HHcy. We found that homocysteine (Hcy) increased the expression of p22phox and p67phox and promoted their recruitment into lipid rafts (indicating the assembly of the NOX complex), thereby increasing ROS generation and NOX activity, NLRP3 inflammasome activation, and pyroptosis. Mechanistically, Hcy activated the NOX-ROS-NLRP3 inflammasome pathway and induced pyroptosis by increasing the expression of acid sphingomyelinase (ASM) to promote the formation of lipid raft clustering. Importantly, lipid raft-mediated pyroptosis was confirmed in HHcy mice, and HHcy-promoted macrophage recruitment in atherosclerotic lesions and HHcy-aggravated AS were blocked by the lipid raft disruptor methyl-β-cyclodextrin. The study findings indicate that Hcy promotes lipid raft clustering via the upregulation of ASM, which mediates the assembly of the NOX complex, causing an increase in ROS generation, NLRP3 inflammasome activation, and pyroptosis, and contributes to HHcy-induced AS.

show abstract

“…Hyperhomocysteinemia can lead to elevated inflammatory factors in blood vessels, damage to the vascular endothelium, and proliferation of vascular smooth muscle cells ( 31 , 32 ). High homocysteine has been reported to promote atherosclerosis and increase the risk of ischemic strokes ( 11 , 33 , 34 ). Because mechanisms such as inflammation are involved in the formation and rupture of IAs, pathological changes caused by homocysteine may contribute to their formation and rupture.…”

Section: Discussionmentioning

confidence: 99%

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study

Zhang²,

Mao³

et al. 2022

Front. Neurol.

View full text Add to dashboard Cite

ObjectiveTo investigate the link between genetic variants associated with plasma homocysteine levels and risk of intracranial aneurysm (IA) using two-sample Mendelian randomization.MethodsWe used single-nucleotide polymorphisms associated with human plasma homocysteine levels as instrumental variables for the primary analysis in a genome-wide association study of 44,147 subjects of European ancestry. Summary-level statistics were obtained for 79,429 individuals, including 7,495 IA cases and 71,934 controls. To enhance validity, five different Mendelian randomization methods (MR-Egger, weighted median, inverse variance weighted, simple mode, and weighted mode) were used for the analyses.ResultsThe inverse variance weighted analysis method produced P-values of 0.398 for aneurysmal subarachnoid hemorrhage [odds ratio (OR): 1.104; 95% confidence interval (CI): 0.878–1.387], 0.246 for IA (OR: 1.124; 95% CI: 0.923–1.368), and 0.644 for unruptured IA (OR: 1.126; 95% CI: 0.682–1.858). The MR-Egger analysis showed no association between IAs and homocysteine, with all P > 0.05.ConclusionUsing gene-related instrumental variables, the Mendelian randomization analyses demonstrated a lack of an association between plasma homocysteine levels and IAs or aneurysmal subarachnoid hemorrhage.

show abstract

miR‐195‐3p alleviates homocysteine‐mediated atherosclerosis by targeting IL‐31 through its epigenetics modifications

Cited by 23 publications

References 49 publications

Hyperhomocysteinemia Is a Predictor for Poor Postoperative Angiogenesis in Adult Patients With Moyamoya Disease

Hyperhomocysteinemia Is a Predictor for Poor Postoperative Angiogenesis in Adult Patients With Moyamoya Disease

HHcy Induces Pyroptosis and Atherosclerosis via the Lipid Raft-Mediated NOX-ROS-NLRP3 Inflammasome Pathway in apoE−/− Mice

Hyperhomocysteinemia and intracranial aneurysm: A mendelian randomization study

Contact Info

Product

Resources

About