Changes in Thyroid Hormone Signaling Mediate Cardiac Dysfunction in the Tg197 Mouse Model of Arthritis: Potential Therapeutic Implications.
Changes in Thyroid Hormone Signaling Mediate Cardiac Dysfunction in the Tg197 Mouse Model of Arthritis: Potential Therapeutic Implications.
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DOI：
10.3390/jcm10235512
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发表时间：
2021-11-25
影响因子：
3.9
通讯作者：
Mourouzis I
中科院分区：
文献类型：
--
作者：
Ntari L;Mantzouratou P;Katsaouni A;Pantos C;Kollias G;Mourouzis I
背景风湿性关节炎（RA）患者显示出更高的心力衰竭风险。本研究探讨了RA小鼠模型中甲状腺激素（TH）信号转导相关的心功能不全的可能原因。方法采用TNF驱动的RA小鼠模型[ThuTNF（Tg197）]。超声心动图评价心功能。测量了左心室（LV）组织中的SERCA 2a和受磷蛋白水平、血清中的甲状腺激素水平、LV中的TH受体和TH相关激酶信号通路。在雌性Tg197小鼠中施用T3激素。结果在Tg197动物中，我们发现左室和心房扩张伴收缩功能障碍，伴有SERCA2a下调。我们认为Tg197心脏中促炎和甲状腺激素信号的相互作用通过增加p38 MAPK和下调TRβ1受体来指示。有趣的是，雌性Tg197小鼠表现出与降低的T3水平和Akt活化相关的更差的心脏表型。T3补充增加Akt激活，恢复SERCA2a表达，改善雌性Tg197小鼠的心脏功能。结论Tg197小鼠TNF过表达通过p38 MAPK激活和TRβ1下调导致心功能不全。T3水平的性别特异性降低可能导致在雌性小鼠中观察到的更差的心脏表型，而T3给药通过修饰的Akt激活改善心脏功能和钙处理。
Background Rheumatoid Arthritis (RA) patients show a higher risk of heart failure. The present study investigated possible causes of cardiac dysfunction related to thyroid hormone (TH) signaling in a RA mouse model. Methods A TNF-driven mouse model of RA[TghuTNF (Tg197)] was used. Cardiac function was evaluated by echocardiography. SERCA2a and phospholamban protein levels in left ventricle (LV) tissue, thyroid hormone levels in serum, TH receptors in LV and TH-related kinase signaling pathways were measured. T3 hormone was administered in female Tg197 mice. Results We show LV and atrial dilatation with systolic dysfunction in Tg197 animals, accompanied by downregulated SERCA2a. We suggest an interaction of pro-inflammatory and thyroid hormone signaling indicated by increased p38 MAPK and downregulation of TRβ1 receptor in Tg197 hearts. Interestingly, female Tg197 mice showed a worse cardiac phenotype related to reduced T3 levels and Akt activation. T3 supplementation increased Akt activation, restored SERCA2a expression and improved cardiac function in female Tg197 mice. Conclusions TNF overexpression of Tg197 mice results in cardiac dysfunction via p38 MAPK activation and downregulation of TRβ1. Gender-specific reduction in T3 levels could cause the worse cardiac phenotype observed in female mice, while T3 administration improves cardiac function and calcium handling via modified Akt activation.
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影响因子：
27.4
作者：
Ntari, Lydia;Sakkou, Maria;Kollias, George
通讯作者：
Kollias, George
影响因子：
4.9
作者：
Innala L;Sjöberg C;Möller B;Ljung L;Smedby T;Södergren A;Magnusson S;Rantapää-Dahlqvist S;Wållberg-Jonsson S
通讯作者：
Wållberg-Jonsson S
影响因子：
3.5
作者：
Corrao, Salvatore;Messina, Silvia;Licata, Giuseppe
通讯作者：
Licata, Giuseppe
影响因子：
11.4
作者：
KEFFER, J;PROBERT, L;KOLLIAS, G
通讯作者：
KOLLIAS, G
DOI：
10.1093/gerona/gly194
发表时间：
2019-06-01
影响因子：
5.1
作者：
Ostan, Rita;Monti, Daniela;Vitale, Giovanni
通讯作者：
Vitale, Giovanni