Aortic aneurysms are a serious health concern as their rupture leads to high morbidity and mortality. Abdominal aortic aneurysms (AAAs) and thoracic aortic aneurysms (TAAs) exhibit differences and similarities in their pathophysiological and pathogenetic features. AAA is a multifactorial disease, mainly associated with atherosclerosis, characterized by a relevant inflammatory response and calcification. TAA is rarely associated with atherosclerosis and in some cases is associated with genetic mutations such as Marfan syndrome (MFS) and bicuspid aortic valve (BAV). MFS-related and non-genetic or sporadic TAA share aortic degeneration with endothelial-to-mesenchymal transition (End-Mt) and fibrosis, whereas in BAV TAA, aortic degeneration with calcification prevails. microRNA (miRNAs) contribute to the regulation of aneurysmatic aortic remodeling. miRNAs are a class of non-coding RNAs, which post-transcriptionally regulate gene expression. In this review, we report the involvement of deregulated miRNAs in the different aortic remodeling characterizing AAAs and TAAs. In AAA, miRNA deregulation appears to be involved in parietal inflammatory response, smooth muscle cell (SMC) apoptosis and aortic wall calcification. In sporadic and MFS-related TAA, miRNA deregulation promotes End-Mt, SMC myofibroblastic phenotypic switching and fibrosis with glycosaminoglycan accumulation. In BAV TAA, miRNA deregulation sustains aortic calcification. Those differences may support the development of more personalized therapeutic approaches.

Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End–MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632–driven End–MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End–MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End–MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients’ blood. Our findings definitively demonstrate that the End–MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.

Objectives: To describe BMI-for-age and transverse dental arch measurements in growing children with Marfan syndrome (MFS) and a non-Marfan pediatric comparison group. Materials and Methods: A retrospective case–control observational study included 41 children aged 6–11 years: 15 patients with MFS (7 males, 8 females; mean age 8.8 ± 1.5 years) and 26 non-Marfan controls (10 males, 16 females; mean age 8.9 ± 1.6 years). Anthropometric parameters and BMI-for-age z-scores were assessed using the WHO 2007 Growth Reference. Digital dental models were used to measure intermolar width (IMW), intercanine width (ICW), and the IMW/ICW ratio. Descriptive statistics, exploratory between-group comparisons, and Pearson correlation analyses were performed. Results: Children with MFS showed significantly lower BMI and BMI-for-age z-scores than controls, although BMI-for-age values generally remained within the normal range. Height values were consistently elevated, reflecting the characteristic growth pattern of MFS. The MFS group showed a significantly smaller mean ICW than controls, whereas the difference in IMW was not statistically significant. The IMW/ICW ratio was also evaluated to characterize transverse dental arch proportions. Pearson correlation analyses showed no significant associations between BMI-for-age z-score and IMW or ICW in either group. In controls, age was positively correlated with BMI-for-age z-score and IMW was positively correlated with ICW; these associations were not observed between BMI-for-age z-score and dental measurements in the MFS group. Conclusions: Children with MFS showed a leaner anthropometric profile and a significantly smaller mean ICW, whereas the difference in IMW was not statistically significant. These preliminary findings should be interpreted cautiously given the small sample size and exploratory nature of the study. Further longitudinal studies with larger cohorts are warranted.

Background: Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 mutations, leading to elastic fiber disarray and early thoracic aortic aneurysm (TAA) formation. Currently, pharmacological treatments lack specificity and only delay progression. We previously reported a specific TGFβ-driven miR-632 up-regulation in MFS TAA tissues and blood causing smooth muscle cell dedifferentiation and aortic wall degeneration. This study evaluated the effects of three conventional antihypertensive drugs (β-blocker, ACE inhibitor and sartan) on parietal remodeling comparing them with a miR-632 inhibitor in an ex vivo TGFβ –induced model of MFS TAA. Methods and Results: Gene expression and western blot analyses demonstrated that only losartan significantly reduced miR-632 and vascular degeneration markers. Notably, combined treatment with ramipril and carvediol compromised losartan’s efficacy, highlighting the need for careful therapeutic selection. miR-632 inhibitor was the most effective strategy in this ex vivo setting, although further preclinical validation is needed to confirm its therapeutic potential in vivo. Conclusions: Our data emphasize that choosing the right treatment in MFS aortopathy requires understanding its specific impact on cellular pathways. Our findings identify losartan as the most effective standard drug while suggesting miR-632 as a promising future target to stabilize the aortic wall and delay surgery.

Background: Marfan syndrome (MFS) is a connective tissue disorder caused by FBN1 mutations, leading to elastic fiber disarray and early thoracic aortic aneurysm (TAA) formation. Currently, pharmacological treatments lack specificity and only delay progression. We previously reported a specific TGFβ-driven miR-632 upregulation in MFS TAA tissues and blood causing smooth muscle cell dedifferentiation and aortic wall degeneration. This study evaluated the effects of three conventional antihypertensive drugs (β-blocker, ACE inhibitor, and sartan) on parietal remodeling, comparing them with a miR-632 inhibitor in an ex vivo TGFβ1-induced model of MFS TAA. Methods and Results: Using an ex vivo paired experimental framework based on independent biological pools of human TAA tissue, gene expression and Western blot analyses demonstrated that only losartan significantly reduced miR-632 and vascular degeneration markers. Notably, combined treatment with ramipril and carvedilol compromised losartan’s efficacy, highlighting the need for careful therapeutic selection. In this ex vivo setting, miR-632 inhibition demonstrated a promising capacity to counteract aortic remodeling, serving as a mechanistic proof-of-concept that warrants further preclinical in vivo validation. Conclusions: Our data emphasize that choosing the right treatment in MFS aortopathy requires understanding its specific impact on cellular pathways. Our findings identify losartan as the most effective standard drug in this model, while suggesting miR-632 as a potential future target to stabilize the aortic wall and, prospectively, delay surgery.