Multi-omics analysis identifies FBXW7 downregulation in hypertensive aorta with experimental validation

Hypertension is a chronic disorder characterized by sustained elevation of systemic arterial blood pressure, which serves as a major risk factor for cardiovascular diseases. Accumulating evidence has indicated an association between the FBXW7 gene and the pathological mechanisms underlying hypertension; however, the specific regulatory pathways and related mechanisms remain to be fully elucidated. FBXW7 was identified as a candidate gene through literature review. Subsequently, Mendelian randomization (MR) analysis was performed to explore its association with hypertension. Meanwhile, single-cell RNA sequencing analysis and cell-cell communication analysis were conducted to investigate potential regulatory mechanisms. Finally, clinical hypertensive patient samples and transverse aortic constriction (TAC) rat models were used to validate FBXW7 protein expression levels. MR analysis with hypertension as the outcome demonstrated that FBXW7 is a relevant exposure factor, further confirmed by sensitivity, heterogeneity, and directionality tests. Single-cell and intercellular signaling analyses suggested that FBXW7 may modulate hypertension progression by participating in angiogenesis, vascular integrity maintenance, and extracellular matrix restructuring. Notably, FBXW7 expression was significantly downregulated in aortic tissues from hypertensive patients; consistent with this, in vivo TAC rat models, examined via immunohistochemistry and Western blot, showed markedly reduced aortic FBXW7 levels in the constricted group compared to controls. Collectively, the findings of this study demonstrate that FBXW7 expression is significantly dysregulated in aortic tissues from both hypertensive patients and TAC rat models. This abnormal expression of FBXW7 is closely associated with the progression of hypertension, which provides a preliminary basis for further exploration of the potential role of FBXW7 in the pathological process of hypertension.