Genetic determinants of vascular remodelling

Abstract

Vascular remodelling is an important physiological mechanism that occurs as a result of changes in hemodynamics, and is a pathological process that plays a major role in the clinical manifestations of cardiovascular diseases. Using a mouse model, it was recently established that vascular remodelling is partially based on ligation of the carotid. In this model, low flow was associated with intima media thickening (IMT). IMT is a major manifestation of atherosclerosis of the carotid artery, and it is an important predictor of cardiovascular events. Carotid IMT has a strong genetic component. It was hypothesized that there would be genetically determined differences in outward remodelling and IMT induced by carotid flow alterations. Vascular remodelling among five inbred strains of mice were compared. Despite similar changes in flow in the left carotid among the strains, dramatic differences in remodelling of the partially ligated left carotid relative to control were observed. IMT correlated significantly with heart rate, outward remodelling and changes in plasminogen activator expression, cell proliferation and apoptosis. There were significant strain-dependent differences in the remodelling index (measured as the ratio of vessel area to IMT), which suggest fundamental alterations in sensing or transducing hemodynamic signals among strains. This model should be useful to identify and characterize the role of genes that mediate vascular remodelling.