Sex-specific regulation of gene expression in the aging monkey aorta
Sex-specific regulation of gene expression in the aging monkey aorta
复制标题
DOI：
10.1152/physiolgenomics.00229.2006
复制
发表时间：
2007-04-24
影响因子：
4.6
通讯作者：
Depre, Christophe
中科院分区：
文献类型：
--
作者：
Qiu, Hongyu;Tian, Bin;Depre, Christophe
尽管血管硬度增加在老年男性中比女性更为突出，而且男性随着年龄的增长更容易患血管疾病，但还没有研究调查可能导致血管衰老性别差异的基因。我们使用猴子模型测试了雄性和雌性对衰老的转录适应不同的假设，该模型不仅在生理学和系统发育上比更常研究的啮齿动物模型更接近人类，而且不受人类衰老过程中最常见形式的血管疾病的影响，例如。例如，动脉粥样硬化、高血压和糖尿病。通过高密度微阵列比较年轻和年老男性或女性（n = 6/组）的主动脉转录谱。当比较年老和年轻的动物时，大约 600 个基因的表达存在差异。令人惊讶的是，男性和女性之间共享的这些基因的比例小于 5%。性别之间的根本差异对于调节细胞外基质的基因尤其明显，这与硬度有关。衰老男性也比女性更容易受到将平滑肌细胞从“收缩”表型转变为“分泌”表型的基因的影响。其他性别差异涉及参与 DNA 修复、应激反应和细胞信号传导的基因。因此，男性和女性在血管老化方面存在基因调控的主要差异，这可能是男性和女性动脉老化的生理差异的基础。此外，对年轻猴子的分析表明，调节血管结构的基因存在差异，这意味着随着衰老而产生的血管硬度的性别差异是在幼年时就被编程的。
Although increased vascular stiffness is more prominent in aging males than females, and males are more prone to vascular disease with aging, no study has investigated the genes potentially responsible for sex differences in vascular aging. We tested the hypothesis that the transcriptional adaptation to aging differs in males and females using a monkey model, which is not only physiologically and phylogenetically closer to humans than the more commonly studied rodent models but also is not afflicted with the most common forms of vascular disease that accompany the aging process in humans, e. g., atherosclerosis, hypertension, and diabetes. The transcriptional profile of the aorta was compared by high-density microarrays between young and old males or females ( n = 6/group). About 600 genes were expressed differentially when comparing old versus young animals. Surprisingly, < 5% of these genes were shared between males and females. Radical differences between sexes were especially apparent for genes regulating the extracellular matrix, which relates to stiffness. Aging males were also more prone than females to genes switching smooth muscle cells from the "contractile" to "secretory" phenotype. Other sex differences involved genes participating in DNA repair, stress response, and cell signaling. Therefore, major differences of gene regulation exist between males and females in vascular aging, which may underlie the physiological differences characterizing aging arteries in males and females. Furthermore, the analyses in young monkeys demonstrated differences in genes regulating vascular structure, implying that the sex differences in vascular stiffness that develop with aging are programmed at an early age.