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Despite its vital importance for establishing proper cardiovascular function, the process through which the vasculature develops and matures postnatally remains poorly understood. From a clinical perspective, an ability to mechanistically model the developmental time course in arteries and veins, as well as to predict how various pathologies and therapeutic interventions alter the affected vessels, promises to improve treatment strategies and long-term clinical outcomes, particularly in pediatric patients suffering from congenital heart defects. In the present study, we conducted a multiscale investigation into the postnatal development of the murine thoracic aorta, examining key allometric relations as well as relationships between in vivo mechanical stresses, collagen and elastin expression, and the gradual accumulation of load-bearing constituents within the aortic wall. Our findings suggest that the production of fibrillar collagens in the developing aorta associates strongly with the ratio of circumferential stresses between systole and diastole, hence emphasizing the importance of a pulsatile mechanobiological stimulus. Moreover, rates of collagen turnover and elastic fiber compaction can be inferred directly by synthesizing transcriptional data and quantitative histological measurements of evolving collagen and elastin content. Consistent with previous studies, we also observed that wall shear stresses acting on the aorta are similar at birth and in maturity, supporting the hypothesis that at least some stress targets are established early in development and maintained thereafter, thus providing a possible homeostatic basis to guide future experiments and inform future predictive modeling., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pregnancy associates with dramatic changes in maternal cardiovascular physiology that ensure that the utero-placental circulation can support the developing fetus. Particularly striking is the marked flow-induced remodeling of uterine arteries during pregnancy and their recovery following birth. Whereas details are available in the literature on alterations in hemodynamics within and changes in the dimensions of uterine arteries during and following pregnancy in mice, we report here the first biaxial biomechanical phenotyping of these arteries during this dynamic period of growth and remodeling (G&R). To gain additional insight into the measured G&R, we also use a computational constrained mixture model to describe and predict findings, including simulations related to complications that may arise during pregnancy. It is found that dramatic pregnancy-induced remodeling of the uterine artery is largely, but not completely, reversed in the postpartum period, which appears to be driven by increases in collagen turnover among other intramural changes. By contrast, data on the remodeling of the ascending aorta, an elastic artery, reveal modest changes that are fully recovered postpartum. There is strong motivation to continue biomechanical studies on this critical aspect of women's health, which has heretofore not received appropriate consideration from the biomechanics community., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Hutchinson-Gilford Progeria Syndrome results in rapid aging and severe cardiovascular sequelae that accelerate near end-of-life. We found a progressive disease process in proximal elastic arteries that was less evident in distal muscular arteries. Changes in aortic structure and function were then associated with changes in transcriptomics assessed via both bulk and single cell RNA sequencing, which suggested a novel sequence of progressive aortic disease: adverse extracellular matrix remodeling followed by mechanical stress-induced smooth muscle cell death, leading a subset of remnant smooth muscle cells to an osteochondrogenic phenotype that results in an accumulation of proteoglycans that thickens the aortic wall and increases pulse wave velocity, with late calcification exacerbating these effects. Increased central artery pulse wave velocity is known to drive left ventricular diastolic dysfunction, the primary diagnosis in progeria children. It appears that mechanical stresses above ~ 80 kPa initiate this progressive aortic disease process, explaining why elastic lamellar structures that are organized early in development under low wall stresses appear to be nearly normal whereas other medial constituents worsen progressively in adulthood. Mitigating early mechanical stress-driven smooth muscle cell loss/phenotypic modulation promises to have important cardiovascular implications in progeria patients., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Arteries can adapt to sustained changes in blood pressure and flow, and it is thought that these adaptive processes often begin with an altered smooth muscle cell activity that precedes any detectable changes in the passive wall components. Yet, due to the intrinsic coupling between the active and passive properties of the arterial wall, it has been difficult to delineate the adaptive contributions of active smooth muscle. To address this need, we used a novel experimental-computational approach to quantify adaptive functions of active smooth muscle in arterial rings excised from the proximal descending thoracic aorta of mice and subjected to short-term sustained circumferential stretches while stimulated with various agonists. A new mathematical model of the adaptive processes was derived and fit to data to describe and predict the effects of active tone adaptation. It was found that active tone was maintained when the artery was adapted close to the optimal stretch for maximal active force production, but it was reduced when adapted below the optimal stretch; there was no significant change in passive behavior in either case. Such active adaptations occurred only upon smooth muscle stimulation with phenylephrine, however, not stimulation with KCl or angiotensin II. Numerical simulations using the proposed model suggested further that active tone adaptation in vascular smooth muscle could play a stabilizing role for wall stress in large elastic arteries.

A new model for the mechanochemical response of smooth muscle is presented. The focus is on the response of the actin-myosin complex and on the related generation of force (or stress). The chemical (kinetic) model describes the cross-bridge interactions with the thin filament in which the calcium-dependent myosin phosphorylation is the only regulatory mechanism. The new mechanical model is based on Hill's three-component model and it includes one internal state variable that describes the contraction/relaxation of the contractile units. It is characterized by a strain-energy function and an evolution law incorporating only a few material parameters with clear physical meaning. The proposed model satisfies the second law of thermodynamics. The results of the combined coupled model are broadly consistent with isometric and isotonic experiments on smooth muscle tissue. The simulations suggest that the matrix in which the actin-myosin complex is embedded does have a viscous property. It is straightforward for implementation into a finite element program in order to solve more complex boundary-value problems such as the control of short-term changes in lumen diameter of arteries due to mechanochemical signals.