Time course of carotid artery growth and remodeling in response to altered pulsatility

Elucidating early time courses of biomechanical responses by arteries to altered mechanical stimuli is paramount to understanding and eventually predicting long-term adaptations. In a previous study, we reported marked long-term (at 35-56 days) consequences of increased pulsatile hemodynamics on arterial structure and mechanics. Motivated by those findings, we focus herein on arterial responses over shorter periods (at 7, 10, and 14 days) following placement of a constrictive band on the aortic arch between the innominate and left carotid arteries of wild-type mice, which significantly increases pulsatility in the right carotid artery. We quantified hemodynamics in vivo using noninvasive ultrasound and measured wall properties and composition in vitro using biaxial mechanical testing and standard (immuno)histology. Compared with both baseline carotid arteries and left carotids after banding, right carotids after banding experienced a significant increase in both pulse pressure, which peaked at day 7, and a pulsatility index for velocity, which continued to rise over the 42-day study despite a transient increase in mean flow that peaked at day 7. Wall thickness and inner diameter also increased significantly in the right carotids, both peaking at day 14, with an associated marked early reduction in the in vivo axial stretch and a persistent decrease in smooth muscle contractility. Glycosaminoglycan content also increased within the wall, peaking at day 14, whereas increases in monocyte chemoattractant protein-1 activity and the collagen-to-elastin ratio continued to rise. These findings confirm that pulsatility is an important modulator of wall geometry, structure, and properties but reveal different early time courses for different microscopic and macroscopic metrics, presumably due to the separate degrees of influence of pressure and flow.