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Moyamoya disease and angiogenesis: a quantitative analysis of key angiogenic markers
Tulika Gupta1, Ranjana Bharti1, Munish Kumar2
1Department of Anatomy, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Abstract:
Moyamoya disease (MMD) is a cerebrovascular condition characterized by progressive narrowing of the internal carotid arteries and their adjacent branches. Aberrant angiogenesis plays a crucial role in its pathogenesis, contributing to both ischemic and hemorrhagic complications. This study aimed to identify potential biomarkers with prognostic value by investigating angiogenic markers in MMD patients. Paired blood and dura mater tissue samples were collected from MMD patients and healthy controls. Using quantitative reverse transcription-polymerase chain reaction, we analysed the expression levels of various angiogenic markers, including vascular endothelial growth factor, Transforming growth factor-β1, Basic fibroblast growth factor, Hypoxia-inducible factor 1-alpha, Platelet-derived growth factor, and Angiopoietin-1. VEGF and TGF-β1 expression were validated at the transcript level (qRT-PCR) in a separate cohort of MMD patients with VEGF further confirmed at the protein level using Enzyme-Linked Immunosorbent Assay. We observed significant increase in expression levels of VEGF, HIF-1α, TGF-β1, bFGF, PDGF and ANG-1 in the dura samples of MMD patients compared to controls. However, in serum samples, only VEGF, TGF-β1, and bFGF were found to be up-regulated. Validation revealed significant upregulation of VEGF and TGF-β1 at the transcript level, with VEGF also markedly elevated at protein level. Study highlights the upregulation of key angiogenic markers in MMD, with VEGF and TGF-β1 showing consistent elevation across tissue and serum samples. These findings suggest their potential role in MMD pathophysiology and as possible biomarkers for disease progression.
Insights
Moyamoya disease (MMD) involves abnormal blood vessel growth. This study found increased levels of key angiogenic markers, vascular endothelial growth factor (VEGF) and Transforming growth factor-β1 (TGF-β1), in MMD patients, suggesting their role in disease progression.
Area of Science:
- Neuroscience
- Vascular Biology
- Biomarker Discovery
Background:
- Moyamoya disease (MMD) is a progressive cerebrovascular disorder.
- Aberrant angiogenesis is implicated in MMD pathogenesis, leading to ischemic and hemorrhagic events.
Purpose of the Study:
- To identify potential prognostic biomarkers in MMD.
- To investigate the expression of angiogenic markers in MMD patients' blood and dura mater.
Main Methods:
- Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) to measure angiogenic marker gene expression.
- Enzyme-Linked Immunosorbent Assay (ELISA) to confirm protein levels.
- Analysis of paired blood and dura mater samples from MMD patients and controls.
Main Results:
- Significantly elevated expression of VEGF, TGF-β1, HIF-1α, bFGF, PDGF, and ANG-1 in MMD dura mater compared to controls.
- Increased serum levels of VEGF, TGF-β1, and bFGF in MMD patients.
- Validation confirmed upregulation of VEGF and TGF-β1 transcripts, and elevated VEGF protein levels.
Conclusions:
- Key angiogenic markers are upregulated in MMD.
- VEGF and TGF-β1 show consistent elevation in both tissue and serum, indicating their potential as MMD biomarkers.
- These markers may play a significant role in MMD pathophysiology and progression.
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