Elevated Expression of TGFB1 in PBMCs Is Associated with Intracranial Aneurysm Formation, but TGFB3 Expression Implicated Rupture

<b>Introduction:</b> The transforming growth factor beta (TGF-β) signaling pathway plays a critical role in cellular processes, including maintaining vascular integrity and regulating vascular remodeling. Aneurysm rupture is associated with pathological changes in the arterial wall. <b>Aims:</b> We aimed to investigate the gene expression of transforming growth factors (<i>TGFB1</i>, <i>TGFB2</i>, <i>TGFB3</i>) in peripheral blood mononuclear cells (PBMCs) isolated from the blood of patients with unruptured intracranial aneurysms (UIAs) and ruptured intracranial aneurysms (RIAs), and from a control group. Additionally, we evaluated serum levels of TGF-β1, TGF-β2, and TGF-β3 and analyzed their associations with various risk factors, including sex, age, aneurysm size, number, shape, smoking, and hypertension. <b>Materials and Methods:</b> The study group consisted of patients diagnosed with intracranial aneurysms (IAs) who were eligible for embolization at the Department of Neurosurgery, Clinical Hospital of the Medical University of Bialystok. The control group consisted of healthy volunteers, recruited from the employees of the Clinical Hospital of the Medical University of Bialystok. Expression levels were assessed using quantitative real-time polymerase chain reaction techniques in PBMCs. Serum concentrations of TGF-β isoforms were evaluated using a multiplexed bead-based immunoassay. <b>Results:</b> Among 32 patients, 24 had unruptured intracranial aneurysms (UIAs), including 18 women and 6 men, while 8 presented with ruptured intracranial aneurysms (RIAs), evenly distributed between women and men (4 each). The mean age of the patients was 53 years (range: 24-71 years). The control group consisted of 20 healthy volunteers, 14 females and 6 males, with a mean age of 51 years (range: 24-71 years). The expression of <i>TGFB1</i> was significantly higher in the IA versus C group, but <i>TGFB3</i> expression was significantly higher in the RIA versus C group. The serum level of TGF-β1 and TGF-β3 was significantly higher in the RIA versus UIA group. Serum TGF-β1 levels were higher in men and individuals < 60 years of age. Positive correlations were observed between serum TGF-β1, TGF-β3 and aneurysm size, with significantly higher TGF-β3 levels in patients with giant aneurysms. <b>Conclusions:</b> Our study highlights the distinct roles of <i>TGFB1</i> and <i>TGFB3</i> in aneurysm pathophysiology, identifying <i>TGFB1</i> as a molecular contributor to aneurysm formation and <i>TGFB3</i> with rupture. Increased serum TGF-β1 and TGF-β3 concentrations could serve as promising noninvasive parameters for assessing the risk of aneurysm rupture. Further research with larger cohorts is needed to define cut-off values and validate the method, enabling the use of blood TGF-β levels as a tool for clinical decision-making.