Effect of an acute mechanical stimulus on aortic structure in the transverse aortic constriction mouse model

Abstract

1. Vascular remodelling is an adaptive response to various stimuli, including mechanical forces, inflammatory cytokines and hormones. In the present study, we investigated histological modification of the aorta and the expression of key proteins participating in vascular remodelling under an acute mechanical stimulus using a transverse aortic constriction (TAC) mouse model. 2. The TAC was performed in male C57BL/6 mice aged 10-12 weeks. A Millar conductance catheter was used to measure cardiac haemodynamic parameters 3 and 14 days after TAC. Aortic structural variations were observed by haematoxylin and eosin, Sirius red and Weigert's elastin staining. Protein levels of Type I collagen, F4/80, α-smooth muscle actin (SMA) and SM22α were analysed by immunohistochemistry. 3. Three days after TAC, the medial area proximal to the aortic band (PA-B) was increased, whereas the area distal to the aortic band (DA-B) was unchanged. There was no difference in luminal area between TAC and sham groups. The adventitia displayed the most significant difference 14 days after TAC: adventitial hyperplasia was abundant and collagen was upregulated in the adventitia of the PA-B with a considerable increase in α-SMA and SM22α. Macrophages accumulated in the adventitia of the PA-B 3 days after TAC and infiltrated into the media and intima of the PA-B 14 days after TAC. 4. In conclusion, the aortic structure undergoes considerable remodelling following an acute mechanical stimulus in the TAC model, mainly in the adventitia. Upregulation of α-SMA and extracellular matrix components accompanied by macrophage infiltration may contribute to adventitial modification in the TAC mouse model.