Mechanisms of Increased Vascular Stiffness Down the Aortic Tree in Aging, Pre-Menopausal Female Monkeys.

OBJECTIVE Protection against increased vascular stiffness in young women is lost after menopause. However, little is known about vascular stiffness in older, pre-menopausal females, because most of the prior work has been conducted in rodents, which live for only 1-3 years and do not go through menopause. The goal of the current investigation was to quantitate differences in stiffness down the aortic tree, and the mechanisms mediating those differences, in older, pre-menopausal (24 ± 0.7 years) vs. young adult (7 ± 0.7 years) female non-human primates. Approach and Results: Aortic stiffness (β), calculated from direct and continuous measurements of aortic diameter and pressure in chronically instrumented, conscious macaque monkeys, increased 2.5-fold in the thoracic aorta, and 5-fold in the abdominal aorta in old pre-menopausal monkeys. The aortic histological mechanisms mediating increased vascular stiffness i.e., collagen/elastin ratio, elastin and collagen disarray and the number of breaks in elastin and collagen fibers were greater in the old pre-menopausal vs. young monkeys, greater in the abdominal vs. the thoracic aorta and greatest in the iliac artery. In addition, more immature and less cross-linked fibers of collagen were found in the aortas of young females. CONCLUSIONS Aortic stiffness increased in old pre-menopausal female monkeys, more so in the abdominal aorta than in the thoracic aorta. Histological mechanisms mediating the increased aortic stiffness were augmented in the old pre-menopausal females, greater in the abdominal vs the thoracic aorta, and greatest in the iliac artery.