Effects of elastin haploinsufficiency on the mechanical behavior of mouse arteries

Abstract

Supravalvular aortic stenosis (SVAS) is associated with decreased elastin and altered arterial mechanics. Mice with a single deletion in the elastin gene (ELN ϩ/Ϫ ) are models for SVAS. Previous studies have shown that elastin haploinsufficiency in these mice causes hypertension, decreased arterial compliance, and changes in arterial wall structure. Despite these differences, ELN ϩ/Ϫ mice have a normal life span, suggesting that the arteries remodel and adapt to the decreased amount of elastin. To test this hypothesis, we performed in vitro mechanical tests on abdominal aorta, ascending aorta, and left common carotid artery from ELN ϩ/Ϫ and wild-type (C57BL/6J) mice. We compared the circumferential and longitudinal stress-stretch relationships and residual strains. The circumferential stress-stretch relationship is similar between genotypes and changes Ͻ3% with longitudinal stretch at lengths within 10% of the in vivo value. At mean arterial pressure, the circumferential stress in the ascending aorta is higher in ELN ϩ/Ϫ than in wild type. Although arterial pressures are higher, the increased number of elastic lamellae in ELN ϩ/Ϫ arteries results in similar tension/lamellae compared with wild type. The longitudinal stress-stretch relationship is similar between genotypes for most arteries. Compared with wild type, the in vivo longitudinal stretch is lower in ELN ϩ/Ϫ abdominal and carotid arteries and the circumferential residual strain is higher in ELN ϩ/Ϫ ascending aorta. The increased circumferential residual strain brings the transmural strain distribution in ELN ϩ/Ϫ ascending aorta close to wild-type values. The mechanical behavior of ELN ϩ/Ϫ arteries is likely due to the reduced elastin content combined with adaptive remodeling during vascular development. stress; residual strain; opening angle; compliance; longitudinal ELASTIN AND COLLAGEN are the principal determinants of passive artery mechanics. Elastin provides reversible extensibility during cyclic loading of the cardiac cycle (22), whereas collagen provides strength and prevents failure at high pressure (11). It is believed that elastin bears load in both the circumferential and longitudinal directions, whereas collagen bears load mostly in the circumferential direction. Elastin is believed responsible for the in vivo longitudinal retraction force in arteries and consequent shortening upon excision. Decreased elastin content with aging, hypertension, and atherosclerosis is accompanied by a decrease in longitudinal retraction force and circumferential compliance (change in diameter for a specified change in pressure) (8). Decreased elastin content also is found in genetic diseases such as supravalvular aortic stenosis (SVAS). SVAS is a congenital narrowing of the large arteries caused by deletions within the elastin gene that lead to functional haploinsufficiency (10). SVAS patients often exhibit hypertension (1) and have thinner and more numerous elastic lamellae (19).Elastin is encoded by a single gene (ELN); hence, the contribution of elastin to pa...

Upregulation of elastase proteins results in aortic dilatation in mucopolysaccharidosis I mice

“…MPS I mice [23] were on a C57BL/6 background and normal controls were heterozygous littermates. Some MPS I mice were injected IV with 10 10 transducing unit (U) U/kg of the retroviral vector hAAT-cIDUA-WPRE at 2-3 days after birth [7].…”

“…Some MPS I mice were injected IV with 10 10 transducing unit (U) U/kg of the retroviral vector hAAT-cIDUA-WPRE at 2-3 days after birth [7]. For compliance curves, periadventitial fat was removed from ascending aortas and the outer diameters determined halfway between the sinotubular junction and the innominate artery [23]. Echocardiography was performed with a Vevo 770 echocardiography machine (VisualSonics, Toronto ON) using inhaled isofluorane anaesthesia.…”

New insights into elastic fiber assembly

“…The vessel wall is thickened at the time of death in these animals and the SMCs are misarranged. Mice having one elastin allele (eln1/2), in contrast, live a normal lifespan despite substantial hypertension and smaller vessels with thinner walls and altered mechanical properties (Wagenseil et al, 2005). Surprisingly, they also have an increased number of lamellar units in the arterial wall (Li et al, 1998b;Faury et al, 2003) (a lamellar unit is defined as a layer of elastin with its associated SMCs).…”

Mechanical Testing of Mouse Carotid Arteries: from Newborn to Adult

“…Example raw pressure, diameter and force data versus time are shown in Figure 8. Single loading cycles with no artifacts are isolated from this data for each protocol (Figure 9), which can then be used for further calculations, analyses and modeling to determine differences in the mechanical behavior between arteries 3,11,15,16 . Table 1.…”

“…3. The deformed outer diameter, unloaded dimensions and axial stretch ratio are necessary to calculate the deformed inner diameter based on conservation of volume 11 . Additional calculations include compliance, stiffness, average stress and average strain 3 .…”