Department of Anesthesiology, The First Hospital of Jilin University, Jilin, China; Department of Health Technology and Informatics, The Hong Kong Polytechnic University, Hong Kong SAR, China.
Department of Anesthesiology, Heyuan People's Hospital, Guangdong, China; Department of Anesthesiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Southern Medical University, Guangdong, China.
Pharmacol Res. 2024 Nov;209:107468. doi: 10.1016/j.phrs.2024.107468. Epub 2024 Oct 18.
Myocardial infarction (MI) remains a leading cause of mortality worldwide. Despite patients with MI benefit from timely reperfusion therapies, the rates of mortality and morbidity remain substantial, suggesting an enduring need for the development of new approaches. Molecular mechanisms underlying myocardial ischemic injury are associated with both cardiomyocytes and non-cardiomyocytes. Exosomes are nano-sized extracellular vesicles released by almost all eukaryotic cells. They facilitate the communication between various cells by transferring information via their cargo and altering different biological activities in recipient cells. Studies have created great prospects for therapeutic applications of exosomes in MI, as demonstrated through their beneficial effect on heart function and reducing ventricular remodeling in association with fibrosis, angiogenesis, apoptosis, and inflammation. Of note, myocardial ischemic injury is primarily due to restricted blood flow, reducing oxygen availability, and causing inefficient utilization of energy substrates. However, the impact of exosomes on cardiac energy metabolism has not been adequately investigated. Although exosomes have been engineered for targeted delivery to enhance clinical efficacy, challenges must be overcome to utilize them reliably in the clinic. In this review, we summarize the research progress of exosomes for MI with a focus on the known and unknown regarding the role of exosomes in energy metabolism in cardiomyocytes and non-cardiomyocytes; as well as potential research avenues of exosome-mitochondrial energy regulation as well as therapeutic challenges. We aim to help identify more efficient molecular targets that may promote the clinical application of exosomes.
心肌梗死（MI）仍然是全球范围内主要的死亡原因。尽管 MI 患者受益于及时的再灌注治疗，但死亡率和发病率仍然很高，这表明仍然需要开发新的方法。心肌缺血损伤的分子机制与心肌细胞和非心肌细胞都有关。外泌体是几乎所有真核细胞释放的纳米大小的细胞外囊泡。它们通过其货物传递信息，并改变受体细胞中的不同生物学活性，从而促进各种细胞之间的通讯。研究为外泌体在 MI 中的治疗应用创造了广阔的前景，因为它们对心脏功能有益，并与纤维化、血管生成、细胞凋亡和炎症有关，减少心室重构。值得注意的是，心肌缺血损伤主要是由于血流受限，降低了氧气的可利用性，并导致能量底物的利用效率降低。然而，外泌体对心脏能量代谢的影响尚未得到充分研究。尽管已经对外泌体进行了工程设计以实现靶向递送，以提高临床疗效，但在临床中可靠地使用外泌体仍需克服一些挑战。在这篇综述中，我们总结了外泌体在 MI 中的研究进展，重点介绍了外泌体在心肌细胞和非心肌细胞能量代谢中的作用的已知和未知，以及外泌体-线粒体能量调节的潜在研究途径和治疗挑战。我们旨在帮助确定更有效的分子靶点，可能促进外泌体的临床应用。
