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

Abstract

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.

Thoracic and abdominal aortas stiffen through unique extracellular matrix changes in intrauterine growth restricted fetal sheep

“…Altered hemodynamics, increases in flow and pressure with the intrinsic stretch, have been shown to increase vascular stiffening and cause vascular remodeling in the mature vasculature (12,16,20). The mechanotransduction pathways for the vascular remodeling have been well established in the adult where small increases in flow have been observed to stimulate production of nitric oxide (NO), prostacyclin, nitric oxide synthase, platelet-derived growth factor receptor (PDGR)-A, platelet-derived growth factor (PDGF)-B, fibroblast growth factor (FGF)-1, FGF-2, TGF-␤, interleukin-1 and -6, and intercellular adhesion molecule-1 while downregulating vascular cell adhesion molecule-1 (21).…”

“…Hemodynamic stress in adult arteries has been shown as an important modulator in vascular ECM composition and stiffness (12,20). The fetal cardiovascular system in utero receives growth and development signaling from hemodynamic forces during the fetal and neonatal period (6,7) and is highly susceptible to abnormal vascular constitutive remodeling due to abnormal hemodynamic stress (1).…”

Mitochondria DNA mutations cause sex-dependent development of hypertension and alterations in cardiovascular function

“…We found that the in vivo axial carotid artery length was smaller in D257A mice (Figure 1G-H). Axial remodeling has been observed in mice with elevated pressures from an aortic banding procedure (Eberth et al, 2010). This length reduction may be a mechanism to compensate for the circumferential remodeling (Humphrey et al, 2009) or simply a result of the higher pressures that cause more circumferential than axial stretch due to known differences in circumferential and axial elastic moduli (Dobrin and Doyle, 1970; Guo and Kassab, 2003; Tanaka and Fung, 1974).…”

“…One mechanism for this relationship is mechanical; arterial stiffening can increase systolic blood pressure via an early return of the reflected pressure waves generated from ventricular ejection (Safar et al, 2003). The resulting increased pressures cause endothelial and smooth muscle cell (SMC) dysfunction and arterial collagen accumulation (Eberth et al, 2010; Lee and Oh, 2010) and subsequently increased ventricular afterload (Kelly et al, 1992), which can eventually lead to heart failure.…”

Computational modeling of hypertensive growth in the human carotid artery

“…The same group also observed that the thickness of the outer lamellar units grew more rapidly than that of the inner units. Eberth et al [10] studied morphological changes in rat carotid arteries for a period of 56 weeks and found an increase in the internal radius from 531 µm to 592 µm, accompanied by an increase in thickness from 23.1 µm to 85.7 µm.…”