Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism.
Obesity alters molecular and functional cardiac responses to ischemia/reperfusion and glucagon-like peptide-1 receptor agonism.
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DOI：
10.1007/s00395-016-0563-4
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发表时间：
2016-07
影响因子：
9.5
通讯作者：
Mather KJ
中科院分区：
文献类型：
--
作者：
Sassoon DJ;Goodwill AG;Noblet JN;Conteh AM;Herring BP;McClintick JN;Tune JD;Mather KJ
本研究验证了肥胖改变心脏对缺血/再灌注和/或胰高血糖素样肽-1（GLP-1）受体激活的反应的假设，并且这些差异与肥胖心脏蛋白质组和microRNA（miR）转录组的改变相关。Ossabaw猪饲喂正常饲料或致肥饲料6个月。在用盐水或exendin-4处理24小时的麻醉猪中，在基线、30分钟冠状动脉闭塞期间和2小时再灌注期间评估心脏功能。从正常和缺血/再灌注区域获得心脏活检。脂肪喂养的动物较重，并表现出高胰岛素血症、高血糖症和高甘油三酯血症。在两组中，缺血/再灌注后血浆肌钙蛋白-I浓度（心肌损伤指数）增加，并通过exendin-4治疗降低。缺血/再灌注导致瘦肉型猪收缩压和每搏输出量降低。这些指数在基线时肥胖心脏中较高，并且在整个缺血/再灌注期间相对维持。Exendin-4给药增加瘦猪的收缩压，但不影响肥胖猪的血压。exendin-4可降低肥胖猪缺血/再灌注后的舒张末期容积。这些不同的生理反应与心肌结构/功能（如肌联蛋白）和钙处理（如SERCA 2a，富含组氨酸的Ca 2+结合蛋白）相关蛋白质的肥胖相关差异相关。肥胖心脏中心脏miR表达的改变包括miR-15、miR-27、miR-130、miR-181和let-7。总之，这些观察结果验证了这种发现方法，并揭示了新的关联，表明以前未发现的机制有助于肥胖对心脏的影响，并有助于缺血/再灌注后GLP-1的作用。
This study tested the hypothesis that obesity alters the cardiac response to ischemia/reperfusion and/or glucagon like peptide-1 (GLP-1) receptor activation, and that these differences are associated with alterations in the obese cardiac proteome and microRNA (miR) transcriptome. Ossabaw swine were fed normal chow or obesogenic diet for 6 months. Cardiac function was assessed at baseline, during a 30-min coronary occlusion, and during 2 hours of reperfusion in anesthetized swine treated with saline or exendin-4 for 24 hours. Cardiac biopsies were obtained from normal and ischemia/reperfusion territories. Fat-fed animals were heavier, and exhibited hyperinsulinemia, hyperglycemia, and hypertriglyceridemia. Plasma troponin-I concentration (index of myocardial injury) was increased following ischemia/reperfusion and decreased by exendin-4 treatment in both groups. Ischemia/reperfusion produced reductions in systolic pressure and stroke volume in lean swine. These indices were higher in obese hearts at baseline and relatively maintained throughout ischemia/reperfusion. Exendin-4 administration increased systolic pressure in lean swine but did not affect blood pressure in obese swine. End-diastolic volume was reduced by exendin-4 following ischemia/reperfusion in obese swine. These divergent physiologic responses were associated with obesity-related differences in proteins related to myocardial structure/function (e.g. titin) and calcium handling (e.g. SERCA2a, histidine-rich Ca2+ binding protein). Alterations in expression of cardiac miRs in obese hearts included miR-15, miR-27, miR-130, miR-181, and let-7. Taken together, these observations validate this discovery approach and reveal novel associations that suggest previously undiscovered mechanisms contributing to the effects of obesity on the heart and contributing to the actions of GLP-1 following ischemia/reperfusion.
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影响因子：
5
作者：
Berwick ZC;Dick GM;Tune JD
通讯作者：
Tune JD
糖尿病性缺血性心力衰竭患者的microRNA失调。
影响因子：
7.7
作者：
Greco S;Fasanaro P;Castelvecchio S;D'Alessandra Y;Arcelli D;Di Donato M;Malavazos A;Capogrossi MC;Menicanti L;Martelli F
通讯作者：
Martelli F
影响因子：
8.2
作者：
Bugger, Heiko;Abel, E. Dale
通讯作者：
Abel, E. Dale
影响因子：
9.5
作者：
Goodwill AG;Tune JD;Noblet JN;Conteh AM;Sassoon D;Casalini ED;Mather KJ
通讯作者：
Mather KJ
影响因子：
8.9
作者：
de Weger, Roel A.;Schipper, Marguerite E. I.;Bovenschen, Niels
通讯作者：
Bovenschen, Niels