Mechanism of gender-specific differences in aortic stiffness with aging in nonhuman primates
Mechanism of gender-specific differences in aortic stiffness with aging in nonhuman primates
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DOI：
10.1161/circulationaha.107.689208
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发表时间：
2007-08-07
期刊：
影响因子：
37.8
通讯作者：
Vatner, Stephen F.
中科院分区：
文献类型：
--
作者：
Qiu, Hongyu;Depre, Christophe;Vatner, Stephen F.
背景-我们的假设是，随着年龄的增长，导致主动脉僵硬的血管特性的变化在年老的雄猴中比在年老的雌猴中更大。方法和结果-我们分析了性别差异在衰老过程中对年轻（年龄，6.6 +/- 0.5岁）和老年（年龄，21.2 +/- 0.2岁）猴子（Macaca fascularis）体内主动脉压和直径测量以及胸主动脉细胞外基质的影响。以压力应变弹性模量（Ep）表示的主动脉硬度，老龄雄猴（5.08 +/- 0.81,P < 0.01）高于老龄雌猴（3.06 +/- 0.52）。在两性中，胶原密度保持不变，胶原结合糖基化终产物增加，1型胶原减少。随着年龄的增长，弹性蛋白密度从22 +/- 1.5%显著降低至15 +/- 1.2% （P < 0.05）。此外，只有老年男性的3型胶原（一种促进弹性的异构体）减少（P < 0.05），而8型胶原（一种促进血管平滑肌细胞新内膜迁移的异构体）增加。与猴子的数据相反，1型和3型胶原蛋白在衰老的大鼠中都显著增加。结论：衰老对主动脉胶原1型和3型的影响存在主要的物种差异。此外，由于老年雄性和雌性猴子的胶原密度、胶原含量、羟脯氨酸和胶原晚期糖基化终产物的变化相似，因此这些因素不能解释老年雄性猴子僵硬程度增加的原因。然而，仅在老年男性中观察到的胶原异构体的变化和弹性蛋白的减少可能是主动脉僵硬增加的主要原因。
Background - Our hypothesis was that the changes in vascular properties responsible for aortic stiffness with aging would be greater in old male monkeys than old female monkeys.Methods and Results - We analyzed the effects of gender differences in aging on in vivo measurements of aortic pressure and diameter and on extracellular matrix of the thoracic aorta in young adult (age, 6.6 +/- 0.5 years) versus old adult (age, 21.2 +/- 0.2 years) monkeys (Macaca fascicularis). Aortic stiffness, as represented by the pressure strain elastic modulus (Ep), increased more in old male monkeys (5.08 +/- 0.81; P < 0.01) than in old females (3.06 +/- 0.52). In both genders, collagen density was maintained, collagen-bound glycation end products increased, and collagen type 1 decreased. However, elastin density decreased significantly (from 22 +/- 1.5% to 15 +/- 1.2%) with aging (P < 0.05) only in males. Furthermore, only old males were characterized by a decrease (P < 0.05) in collagen type 3 (an isoform that promotes elasticity) and an increase in collagen type 8 ( an isoform that promotes the neointimal migration of vascular smooth muscle cells). In contrast to the data in monkeys, collagen types 1 and 3 both increased significantly in aging rats.Conclusions - There are major species differences in the effects of aging on aortic collagen types 1 and 3. Furthermore, because alterations in collagen density, collagen content, hydroxyproline, and collagen advanced glycation end products were similar in both old male and female monkeys, these factors cannot be responsible for the greater increase in stiffness in old males. However, changes in collagen isoforms and the decrease in elastin observed only in old males likely account for the greater increase in aortic stiffness.