Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.
Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.
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DOI：
10.1096/fj.201500057
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发表时间：
2016-05
期刊：
影响因子：
--
通讯作者：
Giussani DA
中科院分区：
文献类型：
--
作者：
Allison BJ;Kaandorp JJ;Kane AD;Camm EJ;Lusby C;Cross CM;Nevin-Dolan R;Thakor AS;Derks JB;Tarry-Adkins JL;Ozanne SE;Giussani DA
衰老和发育编程都与氧化应激和内皮功能障碍有关，表明共同的机制起源。然而，它们之间的相互关系却很少被探讨。在程序性心血管功能障碍的啮齿动物模型中，我们测定了含氧量正常或缺氧妊娠（有或无母体抗氧化剂治疗）的年轻（4个月）和老年（15个月）成年后代的内皮功能和血管端粒长度。我们发现，与含氧正常妊娠的年轻后代相比，老年后代的内皮功能丧失[对乙酰胆碱的最大动脉舒张（71 ± 3比55 ± 3%）和血管短端粒丰度增加（4.2 - 1.3 kb）43.0 ± 1.5比55.1 ± 3.8%）（P <0.05）。妊娠期低血糖会加速年轻后代的内皮功能障碍（对乙酰胆碱的最大动脉舒张：42 ± 1%，P <0.05），但这与血管短端粒长度丰度增加无关。母体别嘌呤醇在常氧或缺氧妊娠的老年后代中挽救了对乙酰胆碱的最大动脉舒张，但在缺氧妊娠的年轻后代中没有。缺氧别嘌呤醇妊娠的老龄后代与未处理缺氧妊娠的老龄后代相比，短端粒（血管短端粒长度丰度35.1 ± 2.5 vs.48.2 ± 2.6%）和血浆促炎趋化因子（24.6 ± 2.8 vs.36.8 ± 5.5 pg/ml，P <0.05）水平较低。这些数据为介导心血管衰老和心血管疾病的发育编程的机制途径的分歧提供了证据，并且即使在出生之前，抗氧化剂也会减缓衰老。艾莉森，B。J.，Kaandorp，J. J.，Kane，A. D、Camm，E. J.，卢斯比，C.，克罗斯角，澳-地M.，内文-多兰，R.，Thakor，A.美国，Derks，J. B.，Tarry-Adkins，J.L.，Ozanne，S. E、Giussani，D. a.心血管衰老和心血管疾病发展程序的机制途径的分歧。
Aging and developmental programming are both associated with oxidative stress and endothelial dysfunction, suggesting common mechanistic origins. However, their interrelationship has been little explored. In a rodent model of programmed cardiovascular dysfunction we determined endothelial function and vascular telomere length in young (4 mo) and aged (15 mo) adult offspring of normoxic or hypoxic pregnancy with or without maternal antioxidant treatment. We show loss of endothelial function [maximal arterial relaxation to acetylcholine (71 ± 3 vs. 55 ± 3%) and increased vascular short telomere abundance (4.2–1.3 kb) 43.0 ± 1.5 vs. 55.1 ± 3.8%) in aged vs. young offspring of normoxic pregnancy (P < 0.05). Hypoxic pregnancy in young offspring accelerated endothelial dysfunction (maximal arterial relaxation to acetylcholine: 42 ± 1%, P < 0.05) but this was dissociated from increased vascular short telomere length abundance. Maternal allopurinol rescued maximal arterial relaxation to acetylcholine in aged offspring of normoxic or hypoxic pregnancy but not in young offspring of hypoxic pregnancy. Aged offspring of hypoxic allopurinol pregnancy compared with aged offspring of untreated hypoxic pregnancy had lower levels of short telomeres (vascular short telomere length abundance 35.1 ± 2.5 vs. 48.2 ± 2.6%) and of plasma proinflammatory chemokine (24.6 ± 2.8 vs. 36.8 ± 5.5 pg/ml, P < 0.05). These data provide evidence for divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease, and aging being decelerated by antioxidants even prior to birth.—Allison, B. J., Kaandorp, J. J., Kane, A. D., Camm, E. J., Lusby, C., Cross, C. M., Nevin-Dolan, R., Thakor, A. S., Derks, J. B., Tarry-Adkins, J. L., Ozanne, S. E., Giussani, D. A. Divergence of mechanistic pathways mediating cardiovascular aging and developmental programming of cardiovascular disease.
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影响因子：
--
作者：
Hardikar S;Song X;Risques RA;Montine TJ;Duggan C;Blount PL;Reid BJ;Anderson GL;Kratz M;White E;Vaughan TL
通讯作者：
Vaughan TL
影响因子：
4.8
作者：
Aiken, Catherine E.;Tarry-Adkins, Jane L.;Ozanne, Susan E.
通讯作者：
Ozanne, Susan E.
影响因子：
5
作者：
Donato AJ;Morgan RG;Walker AE;Lesniewski LA
通讯作者：
Lesniewski LA
DOI：
10.1056/nejmra0903373
发表时间：
2009-12-10
期刊：
The New England journal of medicine
影响因子：
--
作者：
Calado RT;Young NS
通讯作者：
Young NS
影响因子：
3
作者：
Guan, WP;Osanai, T;Okumura, K
通讯作者：
Okumura, K