对右心室对压力负荷的分子和功能反应的连续和区域评估
Kana Yazaki1, Michael Dewar2, John Dauz1
1Division of Cardiology, Labatt Family Heart Centre, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
American journal of physiology. Heart and circulatory physiology
|October 18, 2024
概括
右心室重塑开始于早期的炎症和新陈代谢变化,之前是明显的功能障碍. 对压力负荷的治疗干预应该比目前推的更早地开始.
科学领域:
- 心血管生理学心血管生理学
- 肺高血压研究 肺高血压研究
- 心脏重塑研究的心脏重塑研究
背景情况:
- 在RV压力负载条件下,右心室 (RV) 功能对RV压力负载条件的结果至关重要.
- 了解RV改造的时间和空间方面是优化治疗策略的关键.
- 早期检测和RV改造的干预可以显著影响患者的预后.
研究的目的:
- 描述压力加载开始后的RV改造的时间进程和区域分布.
- 为了研究0至6周肺动脉带化 (PAB) 后RV中发生的分子和细胞变化.
- 在显著的功能衰退开始之前识别RV不适应性重塑的早期指标.
主要方法:
- 老鼠接受了假手术或肺动脉带纹 (PAB),以诱导RV压力过载.
- 进行了心声学和导电性导管检查,以评估RV功能.
- 在PAB后1,3,6周进行了组织学,RNA和分子分析,以评估炎症,纤维化,新陈代谢和亡.
主要成果:
- 一个强烈的炎症反应与增加的细胞因子和巨细胞标志物是显而易见的在1周后PAB.
- 代谢变化,TGF-β1信号传递,原体沉积和亡在1周内显著增加.
- 线粒体功能障碍 (PDK活性增加,PDH酸化降低) 在6周观察到.
- 从PAB后3周开始,显著出现过度缩和缩/放缩功能受损.
结论:
- RV炎症,新陈代谢转变和益纤维细胞信号发生在压力加重的早期,甚至在显著的缩或功能障碍之前.
- 适应性缩和不适应性重塑似乎同时发生.
- 针对不利的RV重塑的治疗干预可能需要比目前实践的更早,在更低的压力值.
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