Sumeet A Khetarpal, John S Millar, Amritha Varshini, Cecilia Vitali, Xuemei Zeng, Paolo Zanoni, Zhiyuan Sun, David Nguyen, James T McParland, Mary G McCoy, Pradeep Natarajan, Marina Cuchel, Leland Mayne, S. W Englander, Sissel Lund-Katz, Michael C Phillips, Nathan A Yates, Sekar Kathiresan and Daniel J Rader
Arteriosclerosis, Thrombosis, and Vascular Biology. 2016;36:A17
A, Chronically instrumented, conscious monkeys were connected to a tether, but otherwise unrestrained in their cage during recording. B, The aorta was instrumented with descending thoracic aortic catheters for measurement of aortic pressure and ultrasonic dimension crystals on opposing surfaces of the thoracic and abdominal aorta for measurement of aortic diameters. Examples of responses to acute phenylephrine–induced hypertension are shown in a young monkey (C) and in old monkey (D). Stiffness reflected by reduced aortic diameter excursion was increased more in old monkeys with phenylephrine than in young monkeys.
In chronically instrumented conscious monkeys, (A) baseline aortic stiffness was greater in old monkeys for both the thoracic and the abdominal aorta, but interestingly abdominal aortic stiffness in young monkeys equaled thoracic aortic stiffness in old monkeys. B, In response to phenylephrine (PE), aortic stiffness was dramatically increased in old monkeys compared with young monkeys. *P<0.05 by ANOVA.
A, Using picrosirius red staining, collagen density was increased more in abdominal aorta of old monkeys compared with abdominal aorta in young monkeys or thoracic aortic collagen in either old or young monkeys. B, Using aldehyde fuchsin staining, elastin density was less in both abdominal aorta compared with the thoracic aorta in both old and young monkeys and decreases were greater in both abdominal and thoracic aorta in old monkeys. C, Collagen to elastin ratio was increased with aging in both thoracic and abdominal aorta, but increases were greater in the abdominal aorta. *P<0.05 by ANOVA.
The disarray of elastin and collagen was subjectively graded in a blinded manner from level 1 as the best to level 10 as the most severe disarray, as shown in Table I from the Materials and Methods section in the online-only Data Supplement. A, The elastin disarray was greater in abdominal aorta vs thoracic aorta for both old and young monkeys and was greater in old monkeys vs young monkeys for both the thoracic and the abdominal aorta. B, The collagen disarray was also greater in old vs young monkeys. Examples of elastin and collagen disarray levels of 1, 5, and 10 are shown in (C). *P<0.05 by Mann–Whitney U test and Kruskal–Wallis test.
Correlation between stiffness and extracellular matrix was compared for (A) collagen density, (B) elastin density, (C) collagen disarray, (D) elastin disarray, and (E) ratio of collagen to elastin density. All parameters showed a linear correlation between stiffness and the extracellular matrix. The best correlations were for elastin disarray and collagen disarray.
Aortic vascular smooth muscle cells (VSMCs) were isolated from young and old male monkeys. The atomic force microscopy force–indentation measurements are directly related to VSMC stiffness. All the individual data are plotted in A, with white squares representing thoracic aorta and white circles for abdominal aorta. The data for young monkeys are on the left and old monkeys on the right. The horizontal lines show the average data for old monkeys and young monkeys. VSMC stiffness was greater in old vs young monkeys, but these differences were not greater in abdominal compared with thoracic aorta, as reflected by the almost complete overlap of data, indicating that this mechanism was not responsible for the greater increases in abdominal aortic stiffness in old monkeys. The average data are shown in B, *P<0.05 by ANOVA.
A, Chronically instrumented, conscious monkeys were connected to a tether, but otherwise unrestrained in their cage during recording. B, The aorta was instrumented with descending thoracic aortic catheters for measurement of aortic pressure and ultrasonic dimension crystals on opposing surfaces of the thoracic and abdominal aorta for measurement of aortic diameters. Examples of responses to acute phenylephrine–induced hypertension are shown in a young monkey (C) and in old monkey (D). Stiffness reflected by reduced aortic diameter excursion was increased more in old monkeys with phenylephrine than in young monkeys.
