Souza Natalia Soares Carvalho, Barenco-Marins Thais, Ferraz Ana Paula, Barbosa Raiana Andrade Quintanilha, Maciel Leonardo, Ponte Cristiano Gonçalves, Seara Fernando Azevedo Cruz, Olivares Emerson Lopes, Nascimento Jose Hamilton Matheus
Instituto de Biofísica Carlos Chagas Filho, Universidade Federal do Rio de Janeiro, 373 Carlos Chagas Filho Avenue, Rio de Janeiro, Brazil.
Campus Professor Geraldo Cidade, Universidade Federal do Rio de Janeiro, Duque de Caxias, Brazil.
Cardiovasc Drugs Ther. 2024 Aug 31. doi: 10.1007/s10557-024-07618-5.
This study is to investigate the repercussions of hypothyroidism in the pathophysiological progression of pulmonary arterial hypertension (PAH).
While the control (CTL, n = 5) male Wistar rats received vehicle, PAH was induced with monocrotaline (MCT group, n = 15). Hypothyroidism was induced in a subset of rats by methimazole 3 weeks prior to the MCT injection (MMZ + MCT group, n = 15). Plasma thyroid hormones were measured by radioimmunoassay. Electrocardiographic, echocardiographic, and hemodynamic analyses were performed to evaluate the progression of PAH. Gene expression of antioxidant enzymes and cardiac hypertrophy markers were assessed by qPCR. Mitochondrial respiration, ATP levels, and ROS production were measured in right ventricular (RV) samples.
Plasma T3 and T4 decreased in both MCT and MMZ + MCT groups (p < 0.05). Right ventricular systolic pressure (RVSP) increased, and RV - dP/dt, + dP/dt, and contractility index decreased in the MCT versus the CTL group and remained within control levels in the MMZ + MCT group (p < 0.05). Relative RV weight, RV wall thickness, RV diastolic area, and relative lung weight were augmented in the MCT versus the CTL group, whereas all parameters were improved to the CTL levels in the MMZ + MCT group (p < 0.05). Only the MCT group exhibited an increased duration of QTc interval compared to the baseline period (p < 0.05). ADP-induced mitochondrial respiration and ATP levels were decreased, and ROS production was increased in MCT versus the CTL group (p < 0.05), while the MMZ + MCT group exhibited increased mitochondrial respiration versus the MCT group (p < 0.05).
Hypothyroidism attenuated the RV mitochondrial dysfunction and the pathophysiological progression of MCT-induced PAH.
本研究旨在探讨甲状腺功能减退在肺动脉高压（PAH）病理生理进展中的影响。
对照组（CTL，n = 5）雄性Wistar大鼠接受溶剂，用野百合碱诱导PAH（MCT组，n = 15）。在MCT注射前3周，用甲巯咪唑在一部分大鼠中诱导甲状腺功能减退（MMZ + MCT组，n = 15）。通过放射免疫测定法测量血浆甲状腺激素。进行心电图、超声心动图和血流动力学分析以评估PAH的进展。通过qPCR评估抗氧化酶和心脏肥大标志物的基因表达。在右心室（RV）样本中测量线粒体呼吸、ATP水平和ROS产生。
MCT组和MMZ + MCT组的血浆T3和T4均降低（p < 0.05）。与CTL组相比，MCT组右心室收缩压（RVSP）升高，RV - dP/dt、+ dP/dt和收缩性指数降低，而MMZ + MCT组保持在对照水平（p < 0.05）。与CTL组相比，MCT组的相对RV重量、RV壁厚度、RV舒张面积和相对肺重量增加，而MMZ + MCT组的所有参数均改善至CTL水平（p < 0.05）。与基线期相比，仅MCT组的QTc间期持续时间增加（p < 0.05）。与CTL组相比，MCT组中ADP诱导的线粒体呼吸和ATP水平降低，ROS产生增加（p < 0.05），而MMZ + MCT组与MCT组相比线粒体呼吸增加（p < 0.05）。
甲状腺功能减退减轻了RV线粒体功能障碍和MCT诱导的PAH的病理生理进展。
