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Abstract Albeit seldom considered explicitly, the vasoactive state of a central artery can contribute to luminal control and thereby affect the in vivo values of flow-induced wall shear stress and pressure-induced intramural stress, which in turn are strong determinants of wall growth and remodeling. Here, we test the hypothesis that diminished vasoactive capacity compromises effective mechano-adaptations of central arteries. Toward this end, we use consistent methods to re-interpret published data on common carotid artery remodeling in a nonpharmacologic mouse model of induced hypertension and a model of connective tissue disorder that results in Marfan syndrome. The mice have identical genetic backgrounds and, in both cases, the data are consistent with the hypothesis considered. In particular, carotid arteries with strong (normal) vasoactive capacity tend to maintain wall thickness and in vivo axial stretch closer to homeostatic, thus resulting in passive circumferential wall stress and energy storage close to normal. We conclude that effective vasoactivity helps to control the biomechanical state in which the cells and matrix turnover, thus helping to delineate mechano-adaptive from maladaptive remodeling. Future analyses of experimental data and computational models of growth and remodeling should account for this strong coupling between smooth muscle contractile capacity and central arterial remodeling.
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Elastin haploinsufficiency in mice has divergent effects on arterial remodeling with aging depending on sex
Elastin is a primary structural protein in the arterial wall that contributes to vascular mechanical properties and degrades with aging. Aging is associated with arterial stiffening and an increase in blood pressure. There is evidence that arterial aging follows different timelines with sex. Our objective was to investigate how elastin content affects arterial remodeling in male and female mice with aging. We used male and female wild-type ( Eln +/+ ) and elastin heterozygous ( Eln +/− ) mice at 6, 12, and 24 mo of age and measured their blood pressure and arterial morphology, wall structure, protein content, circumferential stress, stretch ratio, and stiffness. Two arteries were used with varying contents of elastin: the left common carotid and ascending aorta. We show that Eln +/− arteries start at a different homeostatic set point for circumferential wall stress, stretch, and material stiffness but show similar increases with aging to Eln +/+ mice. With aging, structural stiffness is greatly increased, while material stiffness and circumferential stress are only slightly increased, highlighting the importance of maintaining these homeostatic values. Circumferential stretch shows the smallest change with age and may be important for controlling cellular phenotype. Independent sex differences are mostly associated with males being larger than females; however, many of the measured factors show age × sex and/or genotype × sex interactions, indicating that males and females follow different cardiovascular remodeling timelines with aging and are differentially affected by reduced elastin content. NEW & NOTEWORTHY A comprehensive study on arterial mechanical behavior as a function of elastin content, aging, and sex in mice. Elastin haploinsufficient arteries start at a different homeostatic set point for mechanical parameters such as circumferential stress, stretch, and material stiffness. Structural stiffness of the arterial wall greatly increases with aging, as expected, but there are interactions between sex and aging for most of the mechanical parameters that are important to consider in future work.
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- Award ID(s):
- 1662434
- PAR ID:
- 10285624
- Date Published:
- Journal Name:
- American Journal of Physiology-Heart and Circulatory Physiology
- Volume:
- 319
- Issue:
- 6
- ISSN:
- 0363-6135
- Page Range / eLocation ID:
- H1398 to H1408
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1152/ajpheart.00517.2020
