Expression of SMAD proteins, intracellular effectors of TGF-beta signalling, in non-Marfan patients with thoracic aortic aneurysms and dissections

Abstract

Introduction a role for TGF-beta (TGFb) in thoracic aortic aneurysms and dissections (TAAD) has been evidenced by many studies. For example, around 5% of TAAD patients present Marfan's syndrome (MFS), in which there is a defect in fibrillin, that regulates TGFb signalling. Nevertheless, most TAAD patients have no known syndrome, but rather systemic arterial hypertension (SAH); other alterations in TGFb pathway might be involved in those cases. In this study, we analysed the expression of SMAD proteins, a family of intracellular effectors of TGFb signalling, in TAAD patients without MFS. Since aortic dissections occur always at the external half of the medial layer, we compared both halves. Patients and methods Five micrometre-thick sections of ascending aorta samples obtained at surgery were submitted to immunoperoxidase reactions to detect SMAD-2, -3, -4, and -7. The positive and total cells were counted in each half of the medial layer in the aortas from 10 patients with ascending aorta aneurysms, 10 with aortic dissections (all without MFS, most with SAH), 8 control cases (patients submitted to coronary artery bypass surgery) with SAH, and 9 control cases without SAH. The positive/ total cell ratios in each half of the media were compared by two-way repeated measure ANOVA after ranking transformation (since the distribution was not normal), and Bonferroni t-test as post-hoc test both in all these 4 groups and considering the cases as only two groups (patients with TAAD versus controls). Significance was established in p < or = 0.05. Results No significant difference was detected between halves for any SMAD. No difference was also found considering separately the 4 groups; however, when analyzing TAAD as a whole (table), the expression of SMAD 4 was significantly increased in comparison with controls (p=0.02). Conclusion an increase in SMAD 4 protein, one of the intracellular effectors of TGFb, may be related to TAAD.

TAAD Controls p SMAD 2 0.84 0.86 0.61

SMAD 3 0.62 0.63 0.72

SMAD 4 0.95 0.87 0.02 SMAD 7 0.95 0.95 0.61 Abstract P410 figure Medians for SMAD proteins positive cell/total cell ratio at the medial layer of thoracic aortas with aneurysms or dissections (TAAD) and controls