Department of Cell Biology and Molecular Medicine, Cardiovascular Research Institute, Rutgers, New Jersey Medical School, Newark, New Jersey.
Department of Clinical Sciences, Tufts Cummings School of Veterinary Medicine, North Grafton, Massachusetts.
Am J Physiol Heart Circ Physiol. 2020 Jul 1;319(1):H222-H234. doi: 10.1152/ajpheart.00153.2020. Epub 2020 Jun 12.
Protection against increased vascular stiffness in young women is lost after menopause. However, little is known about vascular stiffness in older, premenopausal females, because most of the prior work has been conducted in rodents, which live for only 1-3 yr 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, premenopausal (24 ± 0.7 yr) versus young adult (7 ± 0.7 yr) female nonhuman primates. 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 fivefold in the abdominal aorta in old premenopausal 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 premenopausal versus young monkeys and greater in the abdominal versus 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. Aortic stiffness increased in old premenopausal 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 premenopausal females, greater in the abdominal versus the thoracic aorta, and greatest in the iliac artery. This is the first study to examine vascular stiffness down the aortic tree in aging premenopausal females (24 ± 0.7 yr old), whereas prior work studied mainly rodents, which are short-lived and do not undergo menopause. Histological mechanisms mediating vascular stiffness in older premenopausal females increased progressively down the aortic tree, with greater increases in the abdominal aorta compared with the thoracic aorta and with the greatest increases and differences observed in the iliac artery.
绝经后，年轻女性的血管僵硬程度的保护作用会丧失。然而，由于之前的大部分研究都是在老鼠身上进行的，而老鼠的寿命只有 1-3 年，并且不会经历更年期，因此对于老年、绝经前的雌性的血管僵硬程度知之甚少。目前的研究目的是定量分析老年、绝经前（24±0.7 岁）与年轻成年（7±0.7 岁）雌性非人类灵长类动物主动脉树中僵硬程度的差异，并分析介导这些差异的机制。通过对慢性仪器化、清醒猕猴的主动脉直径和压力进行直接和连续测量，计算出主动脉僵硬度（β）。在老年绝经前猕猴的胸主动脉和腹主动脉中，主动脉僵硬度分别增加了 2.5 倍和 5 倍。介导血管僵硬程度增加的主动脉组织学机制，即胶原/弹性蛋白比、弹性蛋白和胶原排列紊乱，以及弹性蛋白和胶原纤维断裂的数量，在老年绝经前猕猴中比年轻猕猴更大，在腹主动脉中比胸主动脉更大，在髂动脉中最大。此外，在年轻雌性的主动脉中还发现了更多不成熟和交联较少的胶原纤维。在老年绝经前雌性猕猴中，主动脉僵硬度增加，腹主动脉比胸主动脉增加更明显。在老年绝经前雌性中，介导主动脉僵硬程度增加的组织学机制增强，腹主动脉比胸主动脉更大，髂动脉最大。这是第一项研究老年绝经前雌性（24±0.7 岁）主动脉树中血管僵硬程度的研究，而之前的研究主要集中在老鼠身上，老鼠的寿命较短，并且不会经历更年期。在老年绝经前雌性中，介导血管僵硬的组织学机制沿主动脉树逐渐增加，腹主动脉比胸主动脉增加更明显，髂动脉的增加幅度和差异最大。
