Lee Dae Hyun, Upadhyay Gunjan, Gowda B Gowda Siddabasave, Kain Vasundhara, Malek Md Abdul, Carris Nicholas, Vasaiwala Samip, Yeatman Timothy J, Oliveira Guilherme H, Hui Shu-Ping, Halade Ganesh V
Division of Cardiovascular Sciences, Heart Institute, Department of Internal Medicine, Morsani College of Medicine, University of South Florida, Tampa, Florida, United States.
Morsani College of Medicine, University of South Florida, Tampa, Florida, United States.
Am J Physiol Heart Circ Physiol. 2025 Jun 1;328(6):H1351-H1360. doi: 10.1152/ajpheart.00494.2024. Epub 2024 Dec 20.
Residual inflammation drives atherogenesis to atherosclerosis and myocardial infarction, which triggers acute inflammation. In preclinical studies, polyunsaturated fatty acids-derived specialized pro-resolving mediators (SPMs) have been shown to promote recovery after myocardial infarction (MI), in contrast to proinflammatory lipid mediators (PIMs). However, the dynamic changes of lipid mediators after ST-elevation myocardial infarction (STEMI), particularly after percutaneous coronary intervention (PCI) and respective gene transcripts, are poorly understood. Therefore, the study aimed to assess the early dynamic changes in circulating lipid mediators and lipid pathway transcripts in patients with STEMI who undergo PCI. In this prospective observational clinical study, patients with STEMI ( = 10) and control subjects ( = 6) were included. Plasma samples for lipid mediator profiling (targeted oxylipids) and whole blood for inflammation-related transcript expression were collected at baseline before PCI, 2-, and 24-h post-PCI. A total of 10 patients with STEMI received PCI with a mean age of 53.3 yr, 90% male. Linoleic acid and docosapentaenoic acid levels were higher in patients with STEMI. A subset of PIM levels [hydroxyeicosatetraenoic acids, prostaglandin (PG)E] was elevated at the baseline, with a subsequent decrease in circulating levels at 2 h after PCI [thromboxanes, leukotriene B4 (LTB), 20-hydroxy-LTB]. A subset of SPM levels was elevated at the baseline of STEMI suggestive overlap of inflammation-resolution signaling. The temporal kinetics of lipid mediators showed that both the initiation of inflammation and the resolution process start simultaneously and continue as an endogenous repair mechanism during STEMI. Therefore, approaches to increase these endogenous bioactive resolution mediators content and/or efficacy before PCI should be considered in treating patients with MI. Polyunsaturated fatty acids-derived SPMs are decisive in myocardial infarction (MI) recovery, contrasting with proinflammatory lipid mediators (PIMs). A study on early lipid changes post-percutaneous coronary intervention (PCI) in patients with STEMI shows baseline elevation and post-PCI decrease in PIMs, whereas some SPM levels remain elevated. Findings highlight simultaneous inflammation and resolution in STEMI, emphasizing the need to enhance endogenous repair processes before PCI for better MI treatment.
残余炎症会促使动脉粥样硬化发展为动脉粥样硬化症和心肌梗死，进而引发急性炎症。在临床前研究中，与促炎脂质介质（PIM）相比，多不饱和脂肪酸衍生的特殊促消退介质（SPM）已被证明可促进心肌梗死后的恢复。然而，ST段抬高型心肌梗死（STEMI）后脂质介质的动态变化，尤其是经皮冠状动脉介入治疗（PCI）后以及各自的基因转录本，目前了解甚少。因此，本研究旨在评估接受PCI的STEMI患者循环脂质介质和脂质途径转录本的早期动态变化。在这项前瞻性观察性临床研究中，纳入了STEMI患者（n = 10）和对照受试者（n = 6）。在PCI前基线、PCI后2小时和24小时采集用于脂质介质分析（靶向氧化脂质）的血浆样本以及用于炎症相关转录本表达分析的全血样本。共有10例STEMI患者接受了PCI，平均年龄为53.3岁，90%为男性。STEMI患者的亚油酸和二十二碳五烯酸水平较高。一部分PIM水平[羟基二十碳四烯酸、前列腺素（PG）E]在基线时升高，随后在PCI后2小时循环水平下降[血栓素、白三烯B4（LTB4）、20-羟基-LTB4]。一部分SPM水平在STEMI基线时升高，提示炎症消退信号存在重叠。脂质介质的时间动力学表明，炎症的起始和消退过程同时开始，并在STEMI期间作为一种内源性修复机制持续存在。因此，在治疗心肌梗死患者时，应考虑在PCI前增加这些内源性生物活性消退介质的含量和/或功效的方法。多不饱和脂肪酸衍生的SPM在心肌梗死（MI）恢复中起决定性作用，这与促炎脂质介质（PIM）形成对比。一项关于STEMI患者经皮冠状动脉介入治疗（PCI）后早期脂质变化的研究表明，PIM在基线时升高，PCI后下降，而一些SPM水平仍保持升高。研究结果突出了STEMI中炎症和消退的同时存在，强调了在PCI前加强内源性修复过程以更好地治疗MI的必要性。
