Compromised mechanical homeostasis in arterial aging and associated cardiovascular consequences
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Aging leads to central artery stiffening and associated hemodynamic sequelae. Because healthy arteries exhibit differential geometry, composition, and mechanical behaviors along the central vasculature, we sought to determine whether wall structure and mechanical function differ across five vascular regions—the ascending and descending thoracic aorta, suprarenal and infrarenal abdominal aorta, and common carotid artery—in 20 versus 100-week-old male wild-type mice. Notwithstanding generally consistent changes across these regions, including a marked thickening of the arterial wall, diminished in vivo axial stretch, and loss of elastic energy storage capacity, the degree of changes tended to be slightly greater in abdominal than in thoracic or carotid vessels. Likely due to the long half-life of vascular elastin, most mechanical changes in the arterial wall resulted largely from a distributed increase in collagen, including thicker fibers in the media, and localized increases in glycosaminoglycans. Changes within the central arteries associated with significant increases in central pulse pressure and adverse changes in the left ventricle, including increased cardiac mass and decreased diastolic function. Given the similar half-life of vascular elastin in mice and humans but very different life-spans, there are important differences in the aging of central vessels across these species. Nevertheless, the common finding of aberrant matrix remodeling contributing to a compromised mechanical homeostasis suggests that studies of central artery aging in the mouse can provide insight into mechanisms and treatment strategies for the many adverse effects of vascular aging in humans.
KeywordsArterial stiffness Elastic energy Fibrosis Diastolic function Ventricular hypertrophy
This work was supported, in part, by grants from the National Institutes of Health (R01 HL105297 and P01 HL134605). We thank Nikki Mikush (Staff, Yale School of Medicine) who acquired the ultrasound data and Thomas Stockdale (Visiting Student, University of Cambridge School of Clinical Medicine) who contributed to the early ultrasound analysis.
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Conflicts of interest
All authors declare that they have no conflict of interest.
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