Extracellular Matrix Disarray as a Mechanism for Greater Abdominal Versus Thoracic Aortic Stiffness With Aging in Primates

Abstract

Objective Increased vascular stiffness is central to the pathophysiology of aging, hypertension, diabetes and atherosclerosis. However, relatively few studies have examined vascular stiffness in both the thoracic and abdominal aorta with aging, despite major differences in anatomy, embryological origin and relation to aortic aneurysm. Approach and Results The two other unique features of this study were 1) to study young (9±1 years) and old (26±1 years) male monkeys, and 2) to study direct and continuous measurements of aortic pressure and thoracic and abdominal aortic diameters in conscious monkeys. As expected, aortic stiffness, β, was increased p<0.05, 2–3 fold, in old vs. young thoracic aorta, and augmented further with superimposition of acute hypertension with phenylephrine. Surprisingly, stiffness was not greater in old thoracic aorta than young abdominal aorta. These results can be explained in part by the collagen/elastin ratio, but more importantly, by disarray of collagen and elastin, which correlated best with vascular stiffness. However, vascular smooth muscle cell stiffness, was not different in thoracic vs. abdominal aorta in either young or old monkeys. Conclusions Thus, aortic stiffness increases with aging as expected, but the most severe increases in aortic stiffness observed in the abdominal aorta is novel, where values in young monkeys equaled, or even exceeded, values of thoracic aortic stiffness in old monkeys. These results can be explained by alterations in collagen/elastin ratio, but even more importantly by collagen and elastin disarray.

Killing Me Unsoftly

“…While it remains controversial as to whether increased arterial stiffness precedes or is a consequence of pathologies such as atherosclerosis, 24 a recent study demonstrated that segmental aortic stiffening, and the resultant aortic stiffness gradients, may trigger aortic remodeling leading to abdominal aortic aneurysm (AAA) formation. 25 Complementing these findings, research by Zhang et al conducted in non-human primates indicates that the abdominal segment of aged aortae exhibits the highest regional stiffness 26 – thus making the abdominal aorta a predilection site for aneurysm formation. Furthermore, aortic stiffness is elevated in various connective tissue diseases, including Marfan syndrome, that predispose patients to progressive aortic dilatation, potentially resulting in fatal aortic dissection and death.…”

“…The study by Zhang, et al published in ATVB clearly demonstrated that aortic stiffness increases with age; however, the most severe increases in aortic stiffness were observed in the abdominal aorta, where values in young monkeys equaled or exceeded values of thoracic aortic stiffness in old monkeys. 26 Altogether, these results suggest that regional differences exist between the abdominal and thoracic regions of the aorta that ultimately differentially impact arterial stiffness.…”

Differential Stiffening between the Abdominal and Thoracic Aorta: Effect of Salt Loading in Stroke-Prone Hypertensive Rats

“…This observation is not entirely novel since conflicting trends in aortic scleroprotein contents have long been noted, indicating that other extracellular matrix proteins, cross-linking, glycation, and structural or architectural rearrangement may contribute to altering the mechanical properties of the vascular wall [43]. It was recently shown that scleroprotein disarray as opposed to elastin/collagen ratio changes accounted for the increase in abdominal aortic stiffness versus thoracic stiffness in aged primates [33]. In this study, the authors demonstrated that, as in our salt model, elastin disarrays were more pronounced at the abdominal site and thus may account for the observed increased in stiffness.…”

“…The aorta is often considered as a single entity; however, arterial stiffening develops differently along the aortic bed with aging in both humans and animal models [31-33]. This may be due to the fact that the thoracic and abdominal aorta have different embryologic origins, different means of maturation, and different structural and mechanical properties [34, 35].…”

“…These changes were attributed to differential structural remodeling at each site. More recently, Zhang et al [33] showed that the abdominal aorta is more severely stiffened with age in monkeys and that this was correlated more so with a disarray of collagen and elastin fibers than the traditional measure of the elastin/collagen ratio. The increased stiffness observed at the abdominal level, compared with the thoracic aorta, should be explained first by differences of the geometry of the artery (differential remodeling between the 2 sites) and by the composition of the aortic wall.…”