Postnatal Growth Restriction in Mice Alters Cardiac Protein Composition and Leads to Functional Impairment in Adulthood.
Postnatal Growth Restriction in Mice Alters Cardiac Protein Composition and Leads to Functional Impairment in Adulthood.
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DOI：
10.3390/ijms21249459
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发表时间：
2020-12-12
影响因子：
5.6
通讯作者：
Ferguson DP
中科院分区：
文献类型：
--
作者：
Visker JR;Dangott LJ;Leszczynski EC;Ferguson DP
出生后生长限制（PGR）增加了成年后心血管疾病（CVD）的风险，然而所观察到的病理机制基本原理。本研究的目的是鉴定生长受限和非生长受限小鼠心脏的蛋白质组学差异，并提出与成年期损伤相关的机制。在交配前2周分别饲喂对照组（含20%蛋白质）和低蛋白组（含8%蛋白质）等热量饲料。低脂坝产奶量减少20%，导致生长受限。在出生后（PN1），饲喂CON日粮的幼崽被切换到LP坝（PGR组）或不同的CON坝。在PN21时，对CON （n = 3男性，n = 3女性）和PGR （n = 3男性，n = 3女性）进行安乐死，并通过二维凝胶电泳（2D DIGE）和质谱分析其蛋白质组。Western blotting和硝酸银染色证实2D DIGE结果。实验组：雄性n = 4，雌性n = 4； PGR组：雄性n = 4，雌性n = 4)断奶。在PN77时，超声心动图测量心功能。在PN80时，取出心脏进行免疫印迹检测，以确定这种差异是否会持续到成年。2D DIGE和western blot证实PGR降低了p57kip2、Titin （Ttn）和Collagen （Col）。在PN77时，超声心动图显示PGR心功能受损。在PN80时，p57kip2的western blots显示从PN21恢复的蛋白丰度。大分子量蛋白（Ttn和Col）的PN80银染色在PGR中降低。PGR降低PN21的细胞周期活性，在成年期恢复。然而，胶原纤维网络在成年后发生了变化。
Postnatal growth restriction (PGR) increases the risk for cardiovascular disease (CVD) in adulthood, yet there is minimal mechanistic rationale for the observed pathology. The purpose of this study was to identify proteomic differences in hearts of growth-restricted and unrestricted mice, and propose mechanisms related to impairment in adulthood. Friend leukemia virus B (FVB) mouse dams were fed a control (CON: 20% protein), or low-protein (LP: 8% protein) isocaloric diet 2 weeks before mating. LP dams produce 20% less milk, inducing growth restriction. At birth (postnatal; PN1), pups born to dams fed the CON diet were switched to LP dams (PGR group) or a different CON dam. At PN21, a sub-cohort of CON (n = 3 males; n = 3 females) and PGR (n = 3 males; n = 3 females) were euthanized and their proteome analyzed by two-dimensional differential in-gel electrophoresis (2D DIGE) and mass spectroscopy. Western blotting and silver nitrate staining confirmed 2D DIGE results. Littermates (CON: n = 4 males and n = 4 females; PGR: n = 4 males and n = 4 females) were weaned to the CON diet. At PN77, echocardiography measured cardiac function. At PN80, hearts were removed for western blotting to determine if differences persisted into adulthood. 2D DIGE and western blot confirmation indicated PGR had reductions in p57kip2, Titin (Ttn), and Collagen (Col). At PN77, PGR had impaired cardiac function as measured by echocardiography. At PN80, western blots of p57kip2 showed protein abundance recovered from PN21. PN80 silver staining of large molecular weight proteins (Ttn and Col) was reduced in PGR. PGR reduces cell cycle activity at PN21, which is recovered in adulthood. However, collagen fiber networks are altered into adulthood.
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影响因子：
2.9
作者：
BLUM, H;BEIER, H;GROSS, HJ
通讯作者：
GROSS, HJ
影响因子：
5.5
作者：
Darby, Jack R. T.;McMillen, I. Caroline;Morrison, Janna L.
通讯作者：
Morrison, Janna L.
影响因子：
4.8
作者：
Chattergoon, Natasha N.;Giraud, George D.;Thornburg, Kent L.
通讯作者：
Thornburg, Kent L.
影响因子：
5.6
作者：
Agnoux, Aurore Martin;Antignac, Jean-Philippe;Alexandre-Gouabau, Marie-Cecile
通讯作者：
Alexandre-Gouabau, Marie-Cecile
影响因子：
3.8
作者：
BELL, JM;SLOTKIN, TA
通讯作者：
SLOTKIN, TA