Acute adiponectin delivery is cardioprotective in the aged female rat heart.
Acute adiponectin delivery is cardioprotective in the aged female rat heart.
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DOI：
10.1111/ggi.12306
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发表时间：
2015-05
影响因子：
3.3
通讯作者：
Korzick DH
中科院分区：
文献类型：
--
作者：
Tomicek NJ;Hunter JC;Machikas AM;Lopez V;Korzick DH
老年、绝经后女性心脏的特点是缺血耐受性降低，目前很少有治疗方法来限制缺血性损伤。脂联素（APN）是一种在脂肪组织中产生的细胞因子，在成人心脏缺血再灌注（I/R）损伤后限制梗死面积并改善功能恢复。目的：进一步研究APN对老年雌性大鼠的心脏保护作用。从成年（6-7月龄，n=10）、老年（23月龄，n=14）和老年去卵巢（OVX, n=10）雌性大鼠中分离心脏，进行I/R损伤。缺血时，心脏输注9µg APN或载药。western blotting检测脂联素受体1 （AdipoR1）、AdipoR2和腺苷单磷酸依赖性激酶（AMPK）水平，real - time PCR检测肿瘤坏死因子（TNFα）和烟酰胺腺嘌呤二核苷酸磷酸氧化酶（NOX2/NOX4）水平。对内脏脂肪中的脂联素多聚体进行非还原性western印迹检测。APN输注成功改善各组缺血后左室发育压（~10 ~ 15%），降低各组舒张末期压（EDP）升高（p<0.05）。随着I/R损伤，所有组的phospho-AMPK含量均增加，APN仅在卵巢完好的老年组中增加了phospho-AMPK丰度（p<0.001）。APN不影响年龄相关的缺血前TNFα mRNA升高，而APN在成人和老年OVX中均能减弱NOX 2 mRNA水平。心脏AdipoR2与年龄相关的下降与脂肪中高分子量APN的升高有关。我们的数据表明APN可能是一种保护衰老女性心脏的相关疗法，尽管其机制可能受到与年龄相关的雌激素可用性的影响。
The aged, post-menopausal female heart is characterized by reduced ischemic tolerance, and few therapies currently exist to limit ischemic damage. Adiponectin (APN), a cytokine produced in adipose tissue, limits infarct size and improves functional recovery following ischemia reperfusion (I/R) injury in adult hearts. To extend these previous studies and determine the cardio protective efficacy of APN treatment in aged female rats. hearts were isolated from adult (6–7 mo; n=10), aged (23 mo; n=14), and aged ovariectomized (OVX; n=10) female rats and subjected to I/R injury. Upon ischemia, hearts were infused with 9µg of APN or vehicle. Adiponectin receptor1 (AdipoR1), AdipoR2, and adenosine-monophosphate dependent kinase (AMPK) were assessed by western blotting, tumor necrosis factor (TNFα) and nicotinamide adenine dinucleotide phosphateoxidase (NOX2/NOX4) levels by real time PCR. Non-reducing western blotting for adiponectin multimers in visceral adipose was also performed. APN infusion successfully improved post-ischemic left ventricular developed pressure (~10–15%) and attenuated the rise in end diastolic pressure (EDP) in all groups (p<0.05). With I/R injury, phospho-AMPK increased in all groups with additive effects of APN on increasing phospho-AMPK abundance in aged ovary-intact only (p<0.001). Age-associated increases in preischemic TNFα mRNA were unaffected by APN, while NOX 2 mRNA levels were attenuated by APNin adult and aged OVX. An age-associated decrease in cardiac AdipoR2 was observed in conjunction with elevated high molecular weight APN in adipose. Our data suggest that APN may be a relevant therapy for protecting the aging female heart, albeit through divergent mechanisms which are likely influenced by age-associated estrogen availability.
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影响因子：
4.5
作者：
Korzick, Donna H.;Lancaster, Timothy S.
通讯作者：
Lancaster, Timothy S.
影响因子：
10.8
作者：
Gonon, Adrian T.;Widegren, Ulrika;Pernow, John
通讯作者：
Pernow, John
影响因子：
8.7
作者：
Hotta, K;Funahashi, T;Matsuzawa, Y
通讯作者：
Matsuzawa, Y
影响因子：
5.8
作者：
Gavrila, A;Chan, JL;Mantzoros, CS
通讯作者：
Mantzoros, CS
DOI：
10.1152/ajpendo.00086.2010
发表时间：
2010-11-01
影响因子：
5.1
作者：
Fang, Xiangping;Palanivel, Rengasamy;Sweeney, Gary
通讯作者：
Sweeney, Gary