Laboratory of Cardiovascular Physiology and Reactive Oxygen Species, Department of Physiology, Institute of Basic Health Science, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, Rio Grande do Sul, Brazil.
J Cardiovasc Pharmacol. 2020 Dec;76(6):698-707. doi: 10.1097/FJC.0000000000000923.
Cellular death and survival signaling plays a key role in the progress of adverse cardiac remodeling after acute myocardial infarction (AMI). Therapeutic strategies, such as co-treatment with beta-blocker carvedilol and thyroid hormones (THs), give rise to new approaches that can sustain the cellular homeostasis after AMI. Therefore, we sought to investigate the effects of carvedilol and TH co-administration on apoptosis and survival proteins and on cardiac remodeling after AMI. Male Wistar rats were distributed in 5 groups as follows: sham-operated group (SHAM), infarcted group (MI), infarcted plus carvedilol group (MI+C), infarcted plus TH group (MI+TH), and infarcted plus carvedilol and TH co-treatment group (MI+C+TH). Echocardiographic analysis was performed, and hearts were collected for western blot evaluation. The MI group presented systolic posterior wall thickness loss, an increase in the wall tension index, and an increase in atrial natriuretic peptide tissue levels than the SHAM group. However, in the MI+C+TH group, these parameters were equally to the SHAM group. Moreover, whereas the MI group showed Bax protein expression elevated in relation to the SHAM group, the MI+C+TH group presented Bax reduction and also Akt activation compared with the MI group. In addition, the MI+TH group revealed beta-1 adrenergic receptor (β1AR) upregulation compared with the MI and MI+C groups, whereas the MI+C+TH group presented lower levels of β1AR in relation to the SHAM and MI+TH groups. In conclusion, we suggest that carvedilol and TH co-administration may mediate its cardioprotective effects against adverse cardiac remodeling post-AMI through the Bax reduction, Akt activation, and β1AR decrease.
细胞死亡和存活信号在急性心肌梗死 (AMI) 后不良心脏重构的进展中发挥关键作用。治疗策略，如β受体阻滞剂卡维地洛和甲状腺激素 (THs) 的联合治疗，为维持 AMI 后细胞内稳态提供了新的方法。因此，我们旨在研究卡维地洛和 TH 联合给药对 AMI 后细胞凋亡和存活蛋白以及心脏重构的影响。雄性 Wistar 大鼠分为 5 组：假手术组 (SHAM)、梗死组 (MI)、梗死加卡维地洛组 (MI+C)、梗死加 TH 组 (MI+TH) 和梗死加卡维地洛和 TH 联合治疗组 (MI+C+TH)。进行超声心动图分析，并收集心脏进行 Western blot 评估。与 SHAM 组相比，MI 组出现收缩后壁厚度丧失、壁张力指数增加和心钠肽组织水平升高。然而，在 MI+C+TH 组，这些参数与 SHAM 组相当。此外，与 SHAM 组相比，MI 组 Bax 蛋白表达升高，而与 MI 组相比，MI+C+TH 组 Bax 减少且 Akt 激活。此外，与 MI 和 MI+C 组相比，MI+TH 组β1 肾上腺素能受体 (β1AR) 上调，而与 SHAM 和 MI+TH 组相比，MI+C+TH 组的β1AR 水平较低。总之，我们认为卡维地洛和 TH 联合给药可能通过降低 Bax、激活 Akt 和减少β1AR 介导其对 AMI 后不良心脏重构的保护作用。
