Signaling via the Interleukin-10 Receptor Attenuates Cardiac Hypertrophy in Mice During Pressure Overload, but not Isoproterenol Infusion.
Signaling via the Interleukin-10 Receptor Attenuates Cardiac Hypertrophy in Mice During Pressure Overload, but not Isoproterenol Infusion.
复制标题
DOI：
10.3389/fphar.2020.559220
复制
发表时间：
2020
影响因子：
5.6
通讯作者：
Oceandy D
中科院分区：
文献类型：
--
作者：
Stafford N;Assrafally F;Prehar S;Zi M;De Morais AM;Maqsood A;Cartwright EJ;Mueller W;Oceandy D
炎症在心肌肥厚和心力衰竭的发展过程中起着关键作用。白细胞介素-10（IL-10）是一种主要的抗炎细胞因子，在心脏中表达，并可能在心脏重塑中发挥关键作用。基于IL-10可能减少病理性肥大的证据，假设通过心脏中的IL-10受体（IL 10 R）的信号传导在减少心脏肥大中产生保护作用。本研究旨在探讨IL-10-r1基因敲除对小鼠病理性心肌肥厚的影响。我们发现，在TNF-α诱导的心肌肥大模型中，IL-10 R1基因在培养的心肌细胞中的沉默减弱了IL-10的抗肥大作用。然后，我们分析了IL-10-R1基因缺陷的小鼠（IL-10 R1-/-小鼠），并对它们进行横向主动脉缩窄或异丙肾上腺素输注以诱导病理性肥大。响应于2周的横向主动脉收缩，IL-10 R1-/-小鼠显示出如心脏重量/体重比所示的肥大反应的显著增加，其伴随着心肌细胞表面积和间质纤维化的显著增加。与此相反，有异丙肾上腺素输注（10天）之间的基因敲除和对照组的肥大反应没有差异。使用超声心动图和侵入性血液动力学研究的心脏功能分析未显示WT和IL-10 R1-/-组之间的任何差异，最可能是由于模型的短期性质。总之，我们的数据表明，通过IL-10受体的信号传导可能对压力超负荷诱导的肥大产生保护作用，但对心脏中的β-肾上腺素能刺激没有保护作用。我们的数据支持以前的证据表明，由IL-10及其受体调节的信号可能成为控制病理性心脏肥大的潜在靶点。
Inflammation plays a key role during cardiac hypertrophy and the development of heart failure. Interleukin-10 (IL-10) is a major anti-inflammatory cytokine that is expressed in the heart and may play a crucial role in cardiac remodeling. Based on the evidence that IL-10 potentially reduces pathological hypertrophy, it was hypothesized that signaling via the IL-10 receptor (IL10R) in the heart produces a protective role in reducing cardiac hypertrophy. The aim of this study was to investigate the effects of the ablation of Il-10-r1 gene during pathological cardiac hypertrophy in mice. We found that IL-10R1 gene silencing in cultured cardiomyocytes diminished the anti-hypertrophic effect of Il-10 in TNF-α induced hypertrophy model. We then analyzed mice deficient in the Il-10-r1 gene (IL-10R1-/- mice) and subjected them to transverse aortic constriction or isoproterenol infusion to induce pathological hypertrophy. In response to transverse aortic constriction for 2 weeks, IL-10R1-/- mice displayed a significant increase in the hypertrophic response as indicated by heart weight/body weight ratio, which was accompanied by significant increases in cardiomyocyte surface area and interstitial fibrosis. In contrast, there was no difference in hypertrophic response to isoproterenol infusion (10 days) between the knockout and control groups. Analysis of cardiac function using echocardiography and invasive hemodynamic studies did not show any difference between the WT and IL-10R1-/- groups, most likely due to the short term nature of the models. In conclusion, our data shows that signaling via the IL-10 receptor may produce protective effects against pressure overload-induced hypertrophy but not against β-adrenergic stimuli in the heart. Our data supports previous evidence that signaling modulated by IL-10 and its receptor may become a potential target to control pathological cardiac hypertrophy.
登录
查看更多内容
影响因子：
20.3
作者：
Cassatella, MA;Gasperini, S;Yoshimura, A
通讯作者：
Yoshimura, A
DOI：
10.1161/hypertensionaha.109.148635
发表时间：
2010-08
期刊：
Hypertension (Dallas, Tex. : 1979)
影响因子：
--
作者：
Meléndez GC;McLarty JL;Levick SP;Du Y;Janicki JS;Brower GL
通讯作者：
Brower GL
影响因子：
13.6
作者：
Doroudgar S;Glembotski CC
通讯作者：
Glembotski CC
影响因子：
5
作者：
Kishore R;Krishnamurthy P;Garikipati VN;Benedict C;Nickoloff E;Khan M;Johnson J;Gumpert AM;Koch WJ;Verma SK
通讯作者：
Verma SK
影响因子：
20.1
作者：
Kubota, T;McTiernan, CF;Feldman, AM
通讯作者：
Feldman, AM