Project description:High throughput miRNA microarray screening approach, we compared the miRNA expression pattern in ruptured aneurysm tissues obtained during surgery from patients with aneurysmal subarachnoid hemorrhage (aSAH) with control tissues. Aim was to determine miRNA signature in aneurysmal tissues.
Project description:The molecular mechanisms behind the rupture of intracranial aneurysms remain obscure. MiRNAs are key regulators of a wide array of biological processes altering protein synthesis by binding to target mRNAs. However, variations in miRNA levels in ruptured aneurysmal wall have not been completely examined. We hypothesized that altered miRNA signature in aneurysmal tissues could potentially provide insight into aneurysm pathophysiology. Using a high-throughput miRNA microarray screening approach, we compared the miRNA expression pattern in aneurysm tissues obtained during surgery from patients with aneurysmal subarachnoid hemorrhage (aSAH) with control tissues (GEO accession number GSE161870). We found that the expression of 70 miRNAs was altered. Expressions of the top 10 miRNA were validated, by qRT-PCR and results were correlated with clinical characteristics of aSAH patients. The level of 10 miRNAs (miR-24-3p, miR-26b-5p, miR-27b-3p, miR-125b-5p, miR-143-3p, miR-145-5p, miR-193a-3p, miR-199a-5p, miR-365a-3p/365b-3p, and miR-497-5p) was significantly decreased in patients compared to controls. Expression of miR-125b-5p, miR-143-3p and miR-199a-5p was significantly decreased in patients with poor prognosis and vasospasm. The target genes of few miRNAs were enriched in Transforming growth factor-beta (TGF-β) and Mitogen-activated protein kinases (MAPK) pathways. We found significant negative correlation between the miRNA and mRNA expression (TGF-β1, TGF-β2, SMAD family member 2 (SMAD2), SMAD family member 4 (SMAD4), MAPK1 and MAPK3) in aneurysm tissues. We suggest that miR-26b, miR-199a, miR-497and miR-365, could target multiple genes in TGF-β and MAPK signaling cascades to influence inflammatory processes, extracellular matrix and vascular smooth muscle cell degradation and apoptosis, and ultimately cause vessel wall degradation and rupture.
Project description:Intracranial aneurysm (IA) is a pathological dilation of the cerebral artery which has a potential to rupture leading to sub arachnoid haemorrhage (SAH). One third of the patients with aneurysmal SAH (aSAH) develop symptomatic narrowing of the blood vessels called cerebral vasospasm. The outcomes in the above clinical scenarios are variable and devastating. The study was designed to decipher the molecular mechanisms underlying the pathophysiology of intracranial aneurysm formation, its rupture and subsequent development of vasospasm at the proteomic level. The study was done in two phases – discovery phase and validation phase. We performed iTRAQ-based quantitative proteomic analysis of brain vessel tissue and serum samples in three subgroups of patients with IA and compared them with those of control group (subjects with no cerebrovascular disorder) during the discovery phase. In validation phase, dysregulated proteins of biological significance i.e. ORM1 as a biomarker for unruptured aneurysm and MMP9 as a biomarker for cerebral vasospasm were validated in larger cohort of patients.
Project description:Wall shear stress (WSS) is proposed to influence intracranial aneurysm growth and rupture. Physiological WSS in cerebral arteries is estimated around 20-30 dynes/cm2. The WSS typically observed in human IAs is close to 2 dynes/cm2 for wide-neck aneurysms with a slow recirculating flow and >70 dynes/cm2 in aneurysms with impinging “jet flow”. In this study, we investigated the effects of aneurysmal low and supra-high WSS on endothelial cells.
Project description:Single-molecule level spatial distribution of MERFISH (Multiplexed error-robust fluorescence in situ hybridization) probes targeting 140 genes were analyzed on two control (non-aneurysmal) samples and three TAA samples with Thoracic aortic aneurysm (TAA).
Project description:Gene expression information is useful in prioritizing candidate genes in linkage intervals. The data can also identify pathways involved in the pathophysiology of disease. We used microarrays to identify which genes are expressed in either intracranial arteries (control) or in intracranial aneurysms (case), and can therefore contribute to the disease phenotypes. We used microarrays to identify the pathway membership of expressed genes and the overrepresentation of pathways with expressed genes in the known linkage intervals for intracranial aneurysms. Keywords: Characterization of expression in both diseased and non-diseased intracranial arteries.
Project description:Intracranial pediatric germ cell tumors (GCTs) have different histological differentiations, prognosis and clinical behaviors. Prognosis of patients with germinoma and mature teratoma is good, while patients with other types of GCTs, termed as nongerminomatous malignant germ cell tumors (NGMGCTs), require more extensive drug and irradiation treatment regimen. The mechanisms underlying different prognosis of various GCT subgroups remain elusive. We presented the first miRNA profile of pediatric primary intracranial GCTs.
Project description:Based on sequencing technology to evaluate the differential lncRNA and mRNA expression of intracranial aneurysms. Provide ideas for the study of epigenetic regulation of intracranial aneurysms