The Relevance of Vascular Endothelial Growth Factor, Hypoxia Inducible Factor-1 Alpha, and Clusterin in Carotid Plaque Instability

Basic, Jelena; Stojković, Stefan; Assadian, Afshin; Rauscher, Sabine; Duschek, Nikolaus; Kaun, Christoph; Wojta, Johann; Falkensammer, Juergen

doi:10.1016/j.jstrokecerebrovasdis.2019.03.009

Cited by 13 publications

(9 citation statements)

References 31 publications

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“…In addition, VEGF is critical in the progression of carotid plaque and intraplaque hemorrhage. Symptomatic CAS has a higher expression level of VEGF in atherosclerotic plaques than asymptomatic CAS (Giannoni et al, 2009;Hiyama et al, 2010;Grufman et al, 2014;Basic et al, 2019). Moreover, dendritic cells are crucial regulators of the immune system and are associated with T cell differentiation.…”

Section: Discussionmentioning

confidence: 99%

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis and Phenotyping of Carotid Artery Stenosis

Wang

Liu

et al. 2021

Front. Mol. Biosci.

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Background: Carotid artery stenosis (CAS) is caused by the formation of atherosclerotic plaques inside the arterial wall and accounts for 20–30% of all strokes. The development of an early, noninvasive diagnostic method and the identification of high-risk patients for ischemic stroke is essential to the management of CAS in clinical practice.Methods: We used the data-independent acquisition (DIA) technique to conduct a urinary proteomic study in patients with CAS and healthy controls. We identified the potential diagnosis and risk stratification biomarkers of CAS. And Ingenuity pathway analysis was used for functional annotation of differentially expressed proteins (DEPs). Furthermore, receiver operating characteristic (ROC) analysis was performed to evaluate the diagnostic values of DEPs.Results: A total of 194 DEPs were identified between CAS patients and healthy controls by DIA quantification. The bioinformatics analysis showed that these DEPs were correlated with the pathogenesis of CAS. We further identified 32 DEPs in symptomatic CAS compared to asymptomatic CAS, and biological function analysis revealed that these proteins are mainly related to immune/inflammatory pathways. Finally, a biomarker panel of six proteins (ACP2, PLD3, HLA-C, GGH, CALML3, and IL2RB) exhibited potential diagnostic value in CAS and good discriminative power for differentiating symptomatic and asymptomatic CAS with high sensitivity and specificity.Conclusions: Our study identified novel potential urinary biomarkers for noninvasive early screening and risk stratification of CAS.

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Section: Discussionmentioning

confidence: 99%

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis and Phenotyping of Carotid Artery Stenosis

Wang

Liu

et al. 2021

Front. Mol. Biosci.

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“…After carotid artery stenosis occurs in patients, the intima media of blood vessels thickens, resulting in local tissue hypoxia and inflammation. Under these stimuli, vascular endothelial growth factor is highly expressed, so new blood vessels are formed [ 23 , 24 ]. The plasma Lp-PLA2 level can reflect the level of inflammation, which is mainly secreted by macrophages and lymphocytes in atherosclerotic plaques, and its level indicates the level of arterial plaque inflammation and increased plaque angiogenesis [ 25 ].…”

Section: Discussionmentioning

confidence: 99%

The Relationship between Intracarotid Plaque Neovascularization and Lp (a) and Lp-PLA2 in Elderly Patients with Carotid Plaque Stenosis

Sun

et al. 2022

Disease Markers

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The aim of this study was to investigate the relationship between carotid plaque neovascularization and lipoprotein (a) [Lp (a)], lipoprotein-associated phospholipase A2 (Lp-PLA2) in elderly patients with carotid plaque stenosis. One hundred elderly patients with carotid plaque stenosis diagnosed in our hospital from January 2020 to January 2022 were retrospectively analyzed and divided into stable ( n = 62 ) and unstable ( n = 38 ) groups according to whether the plaque was stable or not. Plasma Lp (a), Lp-PLA2, apoA, and apoB levels were measured; intraplaque angiogenesis (IPN) scores were examined by contrast-enhanced ultrasound (CEUS) to assess IPN grade in patients; and Pearson correlation was used to analyze the relationship between plasma Lp (a) and Lp-PLA2 levels and plaque characteristics and angiogenesis. The maximum thickness and total thickness of carotid plaque in the unstable group were significantly greater than those in the stable group ( P < 0.05 ); the IPN grade was mainly grade III and IV in the unstable group and grade II in the stable group, and the IPN score was significantly higher in the unstable group than in the stable group ( P < 0.05 ); there was no significant difference in the plasma apoA and apoB levels between the two groups ( P > 0.05 ), and the plasma Lp (a) and Lp-PLA2 levels were significantly higher in the unstable group than in the stable group ( P < 0.05 ); the neovascular grade, plasma Lp-PLA2, and Lp (a) levels were significantly increased ( P < 0.05 ); the plasma Lp (a) and Lp-PLA2 levels were positively correlated with the maximum plaque thickness, total plaque thickness, degree of stenosis, and angiogenesis ( P < 0.05 ). The plasma levels of Lp (a) and Lp-PLA2 are positively correlated with intraplaque angiogenesis, and their levels can reflect the stability of carotid plaques.

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“…The results of that study indicated that the serum mRNA levels of HIF-1α in carotid plaque endothelial and smooth muscle cells in symptomatic patients were 1.5-fold higher than those in asymptomatic patients, although no significant difference was observed between the two groups. Notably, the mRNA levels of VEGF were seven times higher in symptomatic patients than in asymptomatic patients ( P = 0.017), indicating a correlation between VEGF and neurological deficits symptoms in patients with symptomatic carotid artery stenosis ( 104 )…”

Section: Functions Of Hif-1α In Different Nvu Cells After Ischemic Strokementioning

confidence: 99%

Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke

Liu

et al. 2021

Front. Immunol.

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Ischemic stroke is caused by insufficient cerebrovascular blood and oxygen supply. It is a major contributor to death or disability worldwide and has become a heavy societal and clinical burden. To date, effective treatments for ischemic stroke are limited, and innovative therapeutic methods are urgently needed. Hypoxia inducible factor-1α (HIF-1α) is a sensitive regulator of oxygen homeostasis, and its expression is rapidly induced after hypoxia/ischemia. It plays an extensive role in the pathophysiology of stroke, including neuronal survival, neuroinflammation, angiogenesis, glucose metabolism, and blood brain barrier regulation. In addition, the spatiotemporal expression profile of HIF-1α in the brain shifts with the progression of ischemic stroke; this has led to contradictory findings regarding its function in previous studies. Therefore, unveiling the Janus face of HIF-1α and its target genes in different type of cells and exploring the role of HIF-1α in inflammatory responses after ischemia is of great importance for revealing the pathogenesis and identifying new therapeutic targets for ischemic stroke. Herein, we provide a succinct overview of the current approaches targeting HIF-1α and summarize novel findings concerning HIF-1α regulation in different types of cells within neurovascular units, including neurons, endothelial cells, astrocytes, and microglia, during the different stages of ischemic stroke. The current representative translational approaches focused on neuroprotection by targeting HIF-1α are also discussed.

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The Relevance of Vascular Endothelial Growth Factor, Hypoxia Inducible Factor-1 Alpha, and Clusterin in Carotid Plaque Instability

Cited by 13 publications

References 31 publications

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis and Phenotyping of Carotid Artery Stenosis

Urinary Proteomics Identifying Novel Biomarkers for the Diagnosis and Phenotyping of Carotid Artery Stenosis

The Relationship between Intracarotid Plaque Neovascularization and Lp (a) and Lp-PLA2 in Elderly Patients with Carotid Plaque Stenosis

Biological Functions and Regulatory Mechanisms of Hypoxia-Inducible Factor-1α in Ischemic Stroke

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