TGFβ1 as a Predictive Biomarker for Collateral Formation Within Ischemic Moyamoya Disease

Chen, Yuanbing; Tang, Miao; Li, Hui; Liu, Hongwei; Wang, Junyu; Huang, Jun

doi:10.3389/fneur.2022.899470

Cited by 7 publications

(4 citation statements)

References 33 publications

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“…[ 44 , 45 , 46 , 47 ]. Vascular endothelial growth factor (VEGF) and platelet-derived growth factor beta polypeptide b (PDGFbb) have been reported to be associated with MMD vessels and have even been applied to the generation of an MMD-like animal model [ 48 , 49 , 50 ]. Our results, for the first time, provide evidence that noncoding RNA circZXDC regulates the VSMC phenotype switch by sponging miR-125a-3p.…”

Section: Discussionmentioning

confidence: 99%

CircZXDC Promotes Vascular Smooth Muscle Cell Transdifferentiation via Regulating miRNA-125a-3p/ABCC6 in Moyamoya Disease

Liu

Huang

Zhang

et al. 2022

Cells

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Moyamoya disease (MMD) is an occlusive, chronic cerebrovascular disease affected by genetic mutation and the immune response. Furthermore, vascular smooth muscle cells (VSMCs) and endothelial cells (ECs) participate in the neointima of MMD, but the etiology and pathophysiological changes in MMD vessels remain largely unknown. Therefore, we established the circZXDC (ZXD family zinc finger C)–miR-125a-3p–ABCC6 (ATP-binding cassette subfamily C member 6) axis from public datasets and online tools based on “sponge-like” interaction mechanisms to investigate its possible role in VSMCs. The results from a series of in vitro experiments, such as dual luciferase reporter assays, cell transfection, CCK-8 assays, Transwell assays, and Western blotting, indicate a higher level of circZXDC in the MMD plasma, especially in those MMD patients with the RNF213 mutation. Moreover, circZXDC overexpression results in a VSMC phenotype switching toward a synthetic status, with increased proliferation and migration activity. CircZXDC sponges miR-125a-3p to increase ABCC6 expression, which induces ERS (endoplasmic reticulum stress), and subsequently regulates VSMC transdifferentiation from the contractive phenotype to the synthetic phenotype, contributing to the intima thickness of MMD vessels. Our findings provide insight into the pathophysiological mechanisms of MMD and indicate that the circZXDC–miR-125a-3p–ABCC6 axis plays a pivotal role in the progression of MMD. Furthermore, circZXDC might be a diagnostic biomarker and an ABCC6-specific inhibitor and has the potential to become a promising therapeutic option for MMD.

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Section: Discussionmentioning

confidence: 99%

CircZXDC Promotes Vascular Smooth Muscle Cell Transdifferentiation via Regulating miRNA-125a-3p/ABCC6 in Moyamoya Disease

Liu

Huang

Zhang

et al. 2022

Cells

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“…Comparatively higher levels of TGFβ1 were observed in the plasma of ischemic MMD patients when compared to individuals with aneurysms and those who are in good health. This finding led to the conclusion that TGFβ1 plays a significant role in promoting collateral formation in ischemic MMD [6]. Cerebral angiography has played a critical role in the diagnosis and grading of MMD.…”

Section: Introductionmentioning

confidence: 99%

Recent Advances for Global Perspectives on Etiology, Pathophysiology, Clinical Presentations, and Management of Moyamoya Disease

Mkwambe,

Zhao,

Deng

2024

WJNS

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Moyamoya disease (MMD) is a condition characterized by the gradual narrowing and blockage of blood vessels in the brain, specifically those in the circle of Willis and the arteries that supply it. This results in reduced blood flow and oxygen to the brain, leading to progressive symptoms and potential complications. The underlying pathophysiological mechanism remains elucidated. However, recent studies have highlighted numerous etiologic factors: abnormal immune complex responses, susceptibility genes, branched-chain amino acids, antibodies, heritable diseases, and acquired diseases, which may be the great potential triggers for the development of moyamoya disease. Its clinical presentation has varying degrees from transient asymptomatic events to significant neurological deficits. Moyamoya disease (MMD) shows different patterns in children and adults. Children with MMD are more susceptible to ischemic events due to decreased blood flow to the brain. Conversely, adults with MMD are more prone to hemorrhagic events involving brain bleeding. Children with MMD may experience a range of symptoms including motor impairments, sensory issues, seizures, headaches, dizziness, cognitive delays, or ongoing neurological problems. Although adults may present with similar clinical symptoms as children, they are more prone to experiencing sudden onset intraventricular, subarachnoid, or intracerebral hemorrhages. One of the challenges in moyamoya disease is the potential for misdiagnosis or delayed diagnosis, particularly when physicians fail to consider MMD as a possible cause in stroke patients. This review aims to provide a comprehensive overview of recent global studies on the pathophysiology of MMD, along with advancements in its management. Additionally, the review will delve into various surgical treatment options for MMD, as well as its rare

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“…In addition to physiological angiogenesis, abnormal or pathological angiogenesis has been implicated in various neurological disorders, including MMD. Recent studies have shown that the dysregulation of angiogenic factors, such as vascular endothelial growth factor (VEGF), angiopoietin‐1, transforming growth factor‐beta 1 and platelet‐derived growth factor could cause abnormal angiogenesis in patients with MMD 6,7 . These angiogenic factors stimulate the proliferative and migratory abilities of ECs and pericytes and promote the production of extracellular matrix (ECM) proteins and new blood vessel formation.…”

Section: Introductionmentioning

confidence: 99%

“…Recent studies have shown that the dysregulation of angiogenic factors, such as vascular endothelial growth factor (VEGF), angiopoietin‐1, transforming growth factor‐beta 1 and platelet‐derived growth factor could cause abnormal angiogenesis in patients with MMD. 6 , 7 These angiogenic factors stimulate the proliferative and migratory abilities of ECs and pericytes and promote the production of extracellular matrix (ECM) proteins and new blood vessel formation. However, the underlying mechanisms of the dysregulation of these angiogenic factors and the aberrant angiogenesis in patients with MMD are poorly understood.…”

Section: Introductionmentioning

confidence: 99%

Bradykinin‐bradykinin receptor (B1R) signalling is involved in the blood–brain barrier disruption in moyamoya disease

Wang,

Sun,

et al. 2023

J Cellular Molecular Medi

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Moyamoya disease (MMD) is a rare disorder of the cerebrovascular system. It is a steno‐occlusive disease that involves angiogenesis and blood–brain barrier (BBB) disruption. Bradykinin (BK), its metabolite des‐Arg9‐BK, and receptor (B1R) affect angiogenesis and BBB integrity. In this study, we aimed to investigate the changes in BK, B1R and des‐Arg9‐BK levels in the serum and brain tissues of patients with MMD and explore the underlying mechanism of these markers in MMD. We obtained the serum samples and superficial temporal artery (STA) tissue of patients with MMD from the Department of Neurosurgery of the Jining First People's Hospital. First, we measured BK, des‐Arg9‐BK and B1R levels in the serum of patients by means of ELISA. Next, we performed immunofluorescence to determine B1R expression in STA tissues. Finally, we determined the underlying mechanism through Western blot, angiogenesis assay, immunofluorescence, transendothelial electrical resistance and transcytosis assays. Our results demonstrated a significant increase in the BK, des‐Arg9‐BK and B1R levels in the serum of patients with MMD compared to healthy controls. Furthermore, an increase in the B1R expression level was observed in the STA tissues of patients with MMD. BK and des‐Arg9‐BK could promote the migratory and proliferative abilities of bEnd.3 cells and inhibited the formation of bEnd.3 cell tubes. In vitro BBB model showed that BK and des‐Arg9‐BK could reduce claudin‐5, ZO‐1 and occluding expression and BBB disruption. To the best of our knowledge, our results show an increase in BK and B1R levels in the serum and STA tissues of patients with MMD. BK and Des‐Arg9‐BK could inhibit angiogenesis, promote migratory and proliferative capacities of cells, and disrupt BBB integrity. Therefore, regulating BK, des‐Arg9‐BK and B1R levels in the serum and the brain could be potential strategies for treating patients with MMD.

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TGFβ1 as a Predictive Biomarker for Collateral Formation Within Ischemic Moyamoya Disease

Cited by 7 publications

References 33 publications

CircZXDC Promotes Vascular Smooth Muscle Cell Transdifferentiation via Regulating miRNA-125a-3p/ABCC6 in Moyamoya Disease

CircZXDC Promotes Vascular Smooth Muscle Cell Transdifferentiation via Regulating miRNA-125a-3p/ABCC6 in Moyamoya Disease

Recent Advances for Global Perspectives on Etiology, Pathophysiology, Clinical Presentations, and Management of Moyamoya Disease

Bradykinin‐bradykinin receptor (B1R) signalling is involved in the blood–brain barrier disruption in moyamoya disease

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