Postgraduate Program in Medicine, Universidade Nove de Julho, UNINOVE, São Paulo, Brazil.
Department of Cardiovascular Physiology, Universidade Federal de São Paulo, São Paulo, Brazil.
Lasers Surg Med. 2022 Aug;54(6):883-894. doi: 10.1002/lsm.23544. Epub 2022 Apr 2.
Ischemic heart disease is the leading cause of death worldwide, and interventions to reduce myocardial infarction (MI) complications are widely researched. Photobiomodulation therapy (PBMT) has altered multiple biological processes in tissues and organs, including the heart.
This study aimed to assess the temporal effects of PBMT on cardiac fibrosis activation after MI in rats. In this proof-of-concept study, we monitored the change in expression patterns over time of genes and microRNAs (miRNAs) involved in the formation of cardiac fibrosis post-MI submitted to PBMT.
Experimental MI was induced, and PBMT was applied shortly after coronary artery ligation (laser light of wavelength 660 nm, 15 mW of power, energy density 22.5 J/cm , 60 seconds of application, irradiated area 0.785 cm , fluence 1.1 J/cm ). Ventricular septal samples were collected at 30 minutes, 3, 6, 24 hours, and 3 days post-MI to determine temporal PBMT's effects on messenger RNA (mRNA) expression associated with cardiac fibrosis activation and miRNAs expression.
PBMT, when applied after ischemia, reversed the changes in mRNA expression of myocardial extracellular matrix genes induced by MI. Surprisingly, PBMT modified cardiac miRNAs expression related to fibrosis replacement in the myocardium. Expression correlations between myocardial mRNAs were assessed. The correlation coefficient between miRNAs and target mRNAs was also determined. A positive correlation was detected among miR-21 and transforming growth factor beta-1 mRNA. The miR-29a expression negatively correlated to Col1a1, Col3a1, and MMP-2 mRNA expressions. In addition, we observed that miR-133 and Col1a1 mRNA were negatively correlated.
The results suggest that PBMT, through the modulation of gene transcription and miRNA expressions, can interfere in cardiac fibrosis activation after MI, mainly reversing the signaling pathway of profibrotic genes.
缺血性心脏病是全球范围内的主要死亡原因，广泛研究了减少心肌梗死 (MI) 并发症的干预措施。光生物调节疗法 (PBMT) 已改变了组织和器官中的多种生物过程，包括心脏。
本研究旨在评估 PBMT 对 MI 后大鼠心脏纤维化激活的时间效应。在这项概念验证研究中，我们监测了 MI 后接受 PBMT 的大鼠心脏纤维化形成过程中相关基因和 microRNA (miRNA) 的表达模式随时间的变化。
诱导实验性 MI，并在冠状动脉结扎后不久应用 PBMT（波长 660nm 的激光，功率 15mW，能量密度 22.5J/cm，应用 60 秒，照射面积 0.785cm，辐照度 1.1J/cm）。MI 后 30 分钟、3、6、24 小时和 3 天采集室间隔样本，以确定 PBMT 在信使 RNA（mRNA）表达上对心肌纤维化激活和 miRNA 表达的时间效应。
缺血后应用 PBMT 逆转了 MI 诱导的心肌细胞外基质基因 mRNA 表达的变化。令人惊讶的是，PBMT 改变了与心肌纤维化替代相关的心脏 miRNA 表达。评估了心肌 mRNA 之间的表达相关性。还确定了 miRNA 和靶 mRNA 之间的相关系数。miR-21 和转化生长因子β-1 mRNA 之间存在正相关。miR-29a 的表达与 Col1a1、Col3a1 和 MMP-2 mRNA 的表达呈负相关。此外，我们观察到 miR-133 和 Col1a1 mRNA 呈负相关。
结果表明，PBMT 通过调节基因转录和 miRNA 表达，可以干扰 MI 后心脏纤维化的激活，主要是逆转促纤维化基因的信号通路。
