Triiodothyronine maintains cardiac transverse-tubule structure and function.
Triiodothyronine maintains cardiac transverse-tubule structure and function.
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DOI：
10.1016/j.yjmcc.2021.06.010
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发表时间：
2021-11
影响因子：
5
通讯作者：
Ojamaa K
中科院分区：
文献类型：
--
作者：
Gilani N;Wang K;Muncan A;Peter J;An S;Bhatti S;Pandya K;Zhang Y;Tang YD;Gerdes AM;Stout RF;Ojamaa K
亚临床甲状腺功能减退症和低T3综合征通常与心血管疾病（CVD）风险和死亡率增加相关。我们研究了T3对T管（TT）结构、Ca2 +动员和收缩性以及二联体蛋白聚集的影响。通过丙硫氧嘧啶（PTU；0.025%）处理成年雌性大鼠8周诱导甲状腺激素（TH）缺乏。然后将大鼠随机分为继续PTU治疗组或三碘 - L - 甲腺原氨酸（T3；10μg/kg/d）治疗2周组（PTU + T3）。在体内超声心动图和血流动力学记录后，分离心肌细胞（CM）以记录Ca2 +瞬变和收缩性。通过共聚焦显微镜评估TT组织，获取STORM图像以测量兰尼碱受体（RyR2）簇的数量和大小以及L型Ca2 +通道（LTCC，Cav1.2）的共定位。使用qPCR和RNA测序分析左心室（LV）组织和培养的心肌细胞中包括两种完整TT蛋白——junctophilin - 2（Jph - 2）和桥连整合因子 - 1（BIN1）在内的表达基因。
所用的T3剂量使血清T3正常化，并逆转了TH缺乏对心脏功能体内指标的不良影响。对分离的心肌细胞的记录表明，T3提高了Ca2 +释放和再摄取的速率，导致肌节缩短和再伸长的速度增加。在TH缺乏的心肌细胞和LV组织中，TT周期性显著降低，横向小管减少但纵向小管增加，并且这些结构通过T3治疗恢复正常。对PTU心肌细胞的STORM数据分析显示，RyR2簇数量减少，每个簇内RyR定位减少，而RyR簇内Cav1.2定位无显著变化。T3治疗使RyR2簇的大小和数量正常化。对LV和培养的心肌细胞的qPCR和RNAseq分析表明，Jph2表达对T3有反应，其随治疗增加可能解释了TT组织和RyR - LTCC偶联的改善。
Subclinical hypothyroidism and low T3 syndrome are commonly associated with an increased risk of cardiovascular disease (CVD) and mortality. We examined effects of T3 on T-tubule (TT) structures, Ca2+ mobilization and contractility, and clustering of dyadic proteins. Thyroid hormone (TH) deficiency was induced in adult female rats by propyl-thiouracil (PTU; 0.025%) treatment for 8 weeks. Rats were then randomized to continued PTU or triiodo-L-thyronine (T3; 10 ug/kg/d) treatment for 2 weeks (PTU+T3). After in vivo echocardiographic and hemodynamic recordings, cardiomyocytes (CM) were isolated to record Ca2+ transients and contractility. TT organization was assessed by confocal microscopy, and STORM images were captured to measure ryanodine receptor (RyR2) cluster number and size, and L-type Ca2+ channel (LTCC, Cav1.2) co-localization. Expressed genes including two integral TT proteins, junctophilin-2 (Jph-2) and bridging integrator-1 (BIN1), were analyzed in left ventricular (LV) tissues and cultured CM using qPCR and RNA sequencing. The T3 dosage used normalized serum T3, and reversed adverse effects of TH deficiency on in vivo measures of cardiac function. Recordings of isolated CM indicated that T3 increased rates of Ca2+ release and re-uptake, resulting in increased velocities of sarcomere shortening and re-lengthening. TT periodicity was significantly decreased, with reduced transverse tubules but increased longitudinal tubules in TH-deficient CMs and LV tissue, and these structures were normalized by T3 treatment. Analysis of STORM data of PTU myocytes showed decreased RyR2 cluster numbers and RyR localizations within each cluster without significant changes in Cav1.2 localizations within RyR clusters. T3 treatment normalized RyR2 cluster size and number. qPCR and RNAseq analyses of LV and cultured CM showed that Jph2 expression was T3-responsive, and its increase with treatment may explain improved TT organization and RyR-LTCC coupling.
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影响因子：
82.9
作者：
通讯作者：
--
DOI：
10.1152/ajpheart.1995.268.4.h1714
发表时间：
1995-04-01
影响因子：
4.8
作者：
ARTMAN, M;ICHIKAWA, H;COETZEE, WA
通讯作者：
COETZEE, WA
影响因子：
3.8
作者：
Hayashi, Tomohiro;Hasegawa, Takuya;Kanzaki, Hideaki;Funada, Akira;Amaki, Makoto;Takahama, Hiroyuki;Ohara, Takahiro;Sugano, Yasuo;Yasuda, Satoshi;Ogawa, Hisao;Anzai, Toshihisa
通讯作者：
Anzai, Toshihisa
影响因子：
20.1
作者：
Gross P;Johnson J;Romero CM;Eaton DM;Poulet C;Sanchez-Alonso J;Lucarelli C;Ross J;Gibb AA;Garbincius JF;Lambert J;Varol E;Yang Y;Wallner M;Feldsott EA;Kubo H;Berretta RM;Yu D;Rizzo V;Elrod J;Sabri A;Gorelik J;Chen X;Houser SR
通讯作者：
Houser SR
影响因子：
9.8
作者：
Hong, Ting-Ting;Smyth, James W.;Shaw, Robin M.
通讯作者：
Shaw, Robin M.