Long-term in vivo resistin overexpression induces myocardial dysfunction and remodeling in rats.
Long-term in vivo resistin overexpression induces myocardial dysfunction and remodeling in rats.
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DOI：
10.1016/j.yjmcc.2011.04.006
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发表时间：
2011-08
影响因子：
5
通讯作者：
Lebeche D
中科院分区：
文献类型：
--
作者：
Chemaly ER;Hadri L;Zhang S;Kim M;Kohlbrenner E;Sheng J;Liang L;Chen J;K-Raman P;Hajjar RJ;Lebeche D
我们之前曾报道，抵抗素会诱导离体大鼠心肌细胞肥大并损害收缩力。为了检查抵抗素对心血管的长期影响，我们使用尾静脉注射的腺相关病毒血清型 9 诱导大鼠体内抵抗素过度表达，并与对照动物进行比较。病毒注射十周后，与对照组相比，抵抗素的过度表达与左心室（LV）重量/体重比率增加相关，增加了收缩末期左心室容积，并显着降低了左心室收缩力（通过左心室压力容积环中的收缩末期压力容积关系斜率来测量）。在分子水平上，抵抗素组中ANF和β-MHC的mRNA表达以及受磷蛋白水平增加，而SERCA2a蛋白表达水平没有变化。在抵抗素过度表达的心脏中观察到组织学纤维化增加，与胶原蛋白、纤连蛋白和结缔组织生长因子的mRNA水平增加相关。抵抗素过度表达还与体内细胞凋亡增加以及体内和体外细胞凋亡分子表型相关。抵抗素过度表达的左心室组织的 TNF-α 受体 1 和 iNOS 水平较高，而 eNOS 水平较低。与对照组相比，体外过表达抵抗素的心肌细胞在培养基中产生大量 TNFα，IκBα 磷酸化增加，细胞内活性氧 (ROS) 含量增加，产生 ROS 的 NADPH 氧化酶的表达和活性增加。长期抵抗素过度表达与大鼠氧化应激、炎症、纤维化、细胞凋亡、心肌重塑和功能障碍的复杂表型相关。这种表型概括了糖尿病心肌病的主要特征。
We have previously reported that resistin induces hypertrophy and impairs contractility in isolated rat cardiomyocytes. To examine the long-term cardiovascular effects of resistin, we induced in vivo overexpression of resistin using adeno-associated virus serotype 9 injected by tail vein in rats and compared to control animals. Ten weeks after viral injection, overexpression of resistin was associated with increased ratio of left ventricular (LV) weight/body weight increased end-systolic LV volume and significant decrease in LV contractility, measured by the end-systolic pressure volume relationship slope in LV pressure volume loops, compared to controls. At the molecular level, mRNA expression of ANF and β-MHC, and protein levels of phospholamban were increased in the resistin group without a change in the level of SERCA2a protein expression. Increased fibrosis by histology, associated with increased mRNA levels of collagen, fibronectin and connective tissue growth factor were observed in the resistin-overexpressing hearts. Resistin overexpression was also associated with increased apoptosis in vivo, along with an apoptotic molecular phenotype in vivo and in vitro. Resistin-overexpressing LV tissue had higher levels of TNF-α receptor 1 and iNOS, and reduced levels of eNOS. Cardiomyocytes overexpressing resistin in vitro produced larger amounts of TNFα in the medium, had increased phosphorylation of IκBα and displayed increased intracellular reactive oxygen species (ROS) content with increased expression and activity of ROS-producing NADPH oxidases compared to controls. Long-term resistin overexpression is associated with a complex phenotype of oxidative stress, inflammation, fibrosis, apoptosis and myocardial remodeling and dysfunction in rats. This phenotype recapitulates key features of diabetic cardiomyopathy.
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影响因子：
3.7
作者：
Nagaev I;Bokarewa M;Tarkowski A;Smith U
通讯作者：
Smith U
DOI：
10.1152/ajpheart.00313.2002
发表时间：
2002-10-01
影响因子：
4.8
作者：
Choi, KM;Zhong, Y;Matlib, MA
通讯作者：
Matlib, MA
DOI：
10.1016/j.bbrc.2008.03.100
发表时间：
2008-05-30
影响因子：
3.1
作者：
Hayata, Nozomi;Fujio, Yasushi;Azuma, Junichi
通讯作者：
Azuma, Junichi
影响因子：
4.8
作者：
Aragno, Manuela;Mastrocola, Raffaella;Boccuzzi, Giuseppe
通讯作者：
Boccuzzi, Giuseppe
影响因子：
3.7
作者：
Panek AN;Posch MG;Alenina N;Ghadge SK;Erdmann B;Popova E;Perrot A;Geier C;Dietz R;Morano I;Bader M;Ozcelik C
通讯作者：
Ozcelik C