Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.).
Department of Medicine, Wilf Family Cardiovascular Research Institute (J.G., U.K., S.S.J., X.W., P.Mo.) and Department of Molecular Pharmacology, Einstein-Sinai Diabetes Research Center (ES-DRC), Institute for Neuroimmunology and Inflammation (INI), Fleischer Institute for Diabetes and Metabolism (FIDAM), Einstein Institute for Aging Research (G.S.), Albert Einstein College of Medicine, New York City, New York; Department of Advanced Biomedical Sciences, International Translational Research and Medical Education (ITME) Consortium, "Federico II" University, Naples, Italy (J.G., D.S., G.S.); Department of Advanced Medical and Surgical Sciences (C.S., R.M., P. Ma., G.P.), and Department of Mental and Physical Health and Preventive Medicine (P.Ma.) University of Campania, Naples, Italy; Infectious Disease Unit, "Sant'Anna and San Sebastiano" Hospital, Caserta, Italy (V.M.)
J Pharmacol Exp Ther. 2023 Jan;384(1):109-115. doi: 10.1124/jpet.122.001209. Epub 2022 Jun 30.
We hypothesized that exosomal microRNAs could be implied in the pathogenesis of thromboembolic complications in coronavirus disease 2019 (COVID-19). We isolated circulating exosomes from patients with COVID-19, and then we divided our population in two arms based on the D-dimer level on hospital admission. We observed that exosomal miR-145 and miR-885 significantly correlate with D-dimer levels. Moreover, we demonstrate that human endothelial cells express the main cofactors needed for the internalization of the "Severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2), including angiotensin converting enzyme 2, transmembrane protease serine 2, and CD-147. Interestingly, human endothelial cells treated with serum from COVID-19 patients release significantly less miR-145 and miR-885, exhibit increased apoptosis, and display significantly impaired angiogenetic properties compared with cells treated with non-COVID-19 serum. Taken together, our data indicate that exosomal miR-145 and miR-885 are essential in modulating thromboembolic events in COVID-19. SIGNIFICANCE STATEMENT: This work demonstrates for the first time that two specific microRNAs (namely miR-145 and miR-885) contained in circulating exosomes are functionally involved in thromboembolic events in COVID-19. These findings are especially relevant to the general audience when considering the emerging prominence of post-acute sequelae of COVID-19 systemic manifestations known as Long COVID.
我们假设细胞外体 microRNAs 可能与 2019 年冠状病毒病 (COVID-19) 的血栓栓塞并发症的发病机制有关。我们从 COVID-19 患者中分离出循环细胞外体，然后根据入院时 D-二聚体水平将人群分为两组。我们观察到细胞外体 miR-145 和 miR-885 与 D-二聚体水平显著相关。此外，我们证明人内皮细胞表达内化“严重急性呼吸综合征冠状病毒 2”(SARS-CoV-2)所需的主要辅助因子，包括血管紧张素转换酶 2、跨膜蛋白酶丝氨酸 2 和 CD-147。有趣的是，与用非 COVID-19 血清处理的细胞相比，用 COVID-19 患者的血清处理的人内皮细胞释放的 miR-145 和 miR-885 明显减少，凋亡增加，血管生成特性明显受损。总之，我们的数据表明，细胞外体 miR-145 和 miR-885 对于调节 COVID-19 中的血栓栓塞事件至关重要。意义陈述：这项工作首次证明，循环细胞外体中包含的两种特定 microRNAs（即 miR-145 和 miR-885）在 COVID-19 的血栓栓塞事件中具有功能相关性。当考虑到被称为长 COVID 的 COVID-19 全身表现的急性后期综合征的新兴重要性时，这些发现对普通受众尤其重要。
