Arteries experience marked variations in blood pressure and flow during the cardiac cycle that can intensify during exercise, in disease, or with aging. Diverse observations increasingly suggest the importance of such pulsatility in arterial homeostasis and adaptations. We used a transverse aortic arch banding model to quantify chronic effects of increased pulsatile pressure and flow on wall morphology, composition, and biaxial mechanical properties in paired mouse arteries: the highly pulsatile right common carotid artery proximal to the band (RCCA-B) and the nearly normal left common carotid artery distal to the band (LCCA-B). Increased pulsatile mechanical stimuli in RCCA-B increased wall thickness compared with LCCA-B, which correlated more strongly with pulse (r* = 0.632; P < 0.01) than mean (r* = 0.020; P = 0.47) or systolic (r* = 0.466; P < 0.05) pressure. Similarly, inner diameter at mean pressure increased in RCCA-B and correlated slightly more strongly with a normalized index of blood velocity pulsatility (r* = 0.915; P < <0.001) than mean flow (r* = 0.834; P < 0.001). Increased wall thickness and luminal diameter in RCCA-B resulted from significant increases in cell number per cross-sectional area (P < 0.001) and collagen-to-elastin ratio (P < 0.05) as well as a moderate (1.7-fold) increase in glycosaminoglycan content, which appears to have contributed to the significant decrease (P < 0.001) in the in-vivo axial stretch in RCCA-B compared with LCCA-B. Changes in RCCA-B also associated with a signficant increase in monocyte chemoattractant protein-1 (P < 0.05) whereas LCCA-B did not. Pulsatile pressure and flow are thus important stimuli in the observed three-dimensional arterial adaptations, and there is a need for increased attention to the roles of both axial wall stress and adventitial remodeling.

Cardiac valve structure and function are primarily determined during early development. Consequently, abnormally-formed heart valves are the most common type of congenital heart defects. Several adult valve diseases can be backtracked to abnormal valve development, making it imperative to completely understand the process and regulation of heart valve development. Epithelial-to-mesenchymal transition (EMT) plays an important role in the development of heart valves. Though hemodynamics is vital to valve development, its role in regulating EMT is still unknown. In this study, intracardiac hemodynamics were altered by constricting the outflow tract (OFT)/ventricle junction (OVJ) of HH16–17 (Hamilton and Hamburger (HH) Stage 16–17) chicken embryos, ex ovo for 24 h. The constriction created an increase in peak and time-averaged centerline velocity along the OFT without changes to volumetric flow or heart rate. Computational fluid dynamics was used to estimate the level of increased spatially-averaged wall shear stresses on the OFT cushion from AMIRA reconstructions. OFT constriction led to a significant decrease in OFT cushion volume and the number of invaded mesenchyme in the OFT cushion. qPCR analysis revealed altered mRNA expression of a representative panel of genes, vital to valve development, in the OFT cushions from banded hearts. This study indicates the importance of hemodynamics in valve development.

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.