Duchatsch Francine, Miotto Danyelle S, Tardelli Lidieli P, Dionísio Thiago J, Campos Dijon S, Santos Carlos F, Okoshi Katashi, Amaral Sandra L
Joint Graduate Program in Physiological Sciences, PIPGCF UFSCar/UNESP, Rodovia Washington Luiz, km 235 Monjolinho, 676, São Carlos 13565-905, SP, Brazil.
Department of Biological Sciences, Bauru School of Dentistry, USP-University of São Paulo, Alameda Octávio Pinheiro Brisolla, 9-75, Bauru 17012-901, SP, Brazil.
Biomedicines. 2023 Dec 5;11(12):3219. doi: 10.3390/biomedicines11123219.
Since cardiac inflammation has been considered an important mechanism involved in heart failure, an anti-inflammatory treatment could control cardiac inflammation and mitigate the worsening of cardiac remodeling. This study evaluated the effects of dexamethasone (DEX) and ramipril treatment on inflammation and cardiac fibrosis in an experimental model of heart failure induced by supravalvular aortic stenosis. Wistar rats (21d) were submitted to an aortic stenosis (AS) protocol. After 21 weeks, an echocardiogram and a maximal exercise test were performed, and after 24 weeks, rats were treated with DEX, ramipril or saline for 14d. The left ventricle (LV) was removed for histological and inflammatory marker analyses. The AS group showed exercise intolerance (-32% vs. Sham), higher relative wall thickness (+63%), collagen deposition and capillary rarefaction, followed by cardiac disfunction. Both treatments were effective in reducing cardiac inflammation, but only DEX attenuated the increased relative wall thickness (-17%) and only ramipril reduced LV fibrosis. In conclusion, both DEX and ramipril decreased cardiac inflammatory markers, which probably contributed to the reduced cardiac fibrosis and relative wall thickness; however, treated AS rats did not show any improvement in cardiac function. Despite the complex pharmacological treatment of heart failure, treatment with an anti-inflammatory could delay the patient's poor prognosis.
由于心脏炎症被认为是心力衰竭的重要机制之一,抗炎治疗可以控制心脏炎症并减轻心脏重塑的恶化。本研究评估了地塞米松(DEX)和雷米普利治疗对由主动脉瓣上狭窄诱导的心力衰竭实验模型中炎症和心脏纤维化的影响。将21日龄的Wistar大鼠进行主动脉狭窄(AS)手术。21周后,进行超声心动图和最大运动试验,24周后,大鼠接受DEX、雷米普利或生理盐水治疗14天。取出左心室进行组织学和炎症标志物分析。AS组表现出运动不耐受(与假手术组相比降低32%)、相对壁厚增加(增加63%)、胶原沉积和毛细血管稀疏,随后出现心脏功能障碍。两种治疗均能有效减轻心脏炎症,但只有DEX减轻了相对壁厚的增加(降低17%),只有雷米普利减少了左心室纤维化。总之,DEX和雷米普利均降低了心脏炎症标志物,这可能有助于减少心脏纤维化和相对壁厚;然而,治疗后的AS大鼠心脏功能未显示任何改善。尽管心力衰竭的药物治疗复杂,但抗炎治疗可能会延缓患者的不良预后。