Analysis of FBN1, TGFβ2, TGFβR1 and TGFβR2 mRNA as Key Molecular Mechanisms in the Damage of Aortic Aneurysm and Dissection in Marfan Syndrome

Marfan syndrome (MFS) is an inherited connective tissue disorder, with aortic root aneurysm and/or dissection being the most severe and life-threatening complication. These conditions have been linked to pathogenic variants in the <i>FBN1</i> gene and dysregulated <i>TGFβ</i> signaling. Our objective was to evaluate the mRNA expression of <i>FBN1</i>, <i>TGFBR1</i>, <i>TGFBR2</i>, and <i>TGFB2</i> in aortic tissue from MFS patients undergoing surgery for aortic dilation. This prospective study (2014-2023) included 20 MFS patients diagnosed according to the 2010 Ghent criteria, who underwent surgery for aneurysm or dissection based on Heart Team recommendations, along with 20 non-MFS controls. RNA was extracted, and mRNA levels were quantified using RT-qPCR. Patients with dissection showed significantly higher <i>FBN1</i> mRNA levels [79 (48.1-110.1)] compared to controls [37.2 (25.1-79)] (<i>p</i> = 0.03). Conversely, <i>TGFB2</i> expression was significantly lower in MFS patients [12.17 (6.54-24.70)] than in controls [44.29 (25.85-85.36)] (<i>p</i> = 0.029). A positive correlation was observed between higher <i>FBN1</i> expression and a larger sinotubular junction diameter (r = 0.42, <i>p</i> = 0.07), while increased <i>FBN1</i> expression was particularly evident in MFS patients with dissection. Additionally, <i>TGFB2</i> expression showed an inverse correlation with ascending aortic diameter (r = 0.53, <i>p</i> = 0.01). In aortic tissue, we found decreased <i>TGFB2</i> and receptor levels alongside increased <i>FBN1</i> mRNA levels. These molecular alterations may reflect compensatory mechanisms in response to tissue damage caused by mechanical stress, leading to dysregulation of physiological signaling pathways and ultimately contributing to aortic dilation in MFS.