期刊
EXPERIMENTAL GERONTOLOGY
卷 83, 期 -, 页码 165-170出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.exger.2016.08.007
关键词
MicroRNA; Age related arterial dysfunction; Endothelial dependent dilation
资金
- National Institute of Aging [R01 AG048366, R21 AG033755, R01 AG040297, K02 AG045339]
- National Heart, Lung, and Blood Institute at the National Institutes of Health [PO1 HL1091830]
- United States (U.S.) Department of Veterans Affairs Biomedical Laboratory Research and Development Service [1I01BX002151]
- Veteran's Affairs Rehabilitation Research and Development Service [E6910-R, E1697-R, E1433-P, E9275-L]
MicroRNAs (miRs) are small non-coding RNAs that are important regulators of aging and cardiovascular diseases. MiR-92a is important in developmental vascular growth and tumorigenesis and two of its putative targets, tumor necrosis factor alpha receptor 1 (TNFR1) and collagen type 1, play a role in age-related arterial dysfunction. We hypothesized that reduced miR-92a expression contributes to age-related arterial dysfunction characterized by endothelial dysfunction and increased large artery stiffness. MiR-92a is reduced 39% (RT-PCR, p < 0.05) in arteries of older adults compared to young adults. Similarly, there was a 40% reduction in miR-92a in aortas of old (29 months, n = 13) compared to young (6 months, n = 11) B6D2F1 mice, an established model of vascular aging. To determine if reduced miR-92a contributes to arterial dysfunction; miR-92a was inhibited in vivo in young mice using antagomirs (I.P., 4 wks). Antagomir treatment was associated with a concomitant 48% increase in TNFR1 (Western blot, p < 0.05), 19% increase in type 1 collagen (immunohistochemistry, p < 0.01), and a reduction in endothelial dependent dilation (max dilation: 93 +/- 1 vs. 73 +/- 5%, p < 0.01) in response to acetylcholine (ACh, 10(-9) to 10(-4) M). Treatment with the nitric oxide (NO) synthase inhibitor, L-NAME (10-4 M), revealed that impaired ACh dilation after antagomir treatment resulted from reduced NO bioavailability. Inhibition of miR-92a also increased arterial stiffness (pulse wave velocity, 309 +/- 13 vs. 484 +/- 52 cm/s, p < 0.05). Together, these results suggest that experimental reductions in arterial miR-92a partially mimic the arterial aging phenotype and we speculate that modulating miR-92a may provide a therapeutic strategy to improve age-related arterial dysfunction. (C) 2016 Elsevier Inc. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据