Silva Vicente R, Neves Eula G A, Passos Lívia S Araújo, Cristina de Melo Flávia, Teixeira-Carvalho Andrea, Nassif Maria Cecília L, Junqueira Lucas Lodi, Aikawa Elena, Dutra Walderez O, Nunes Maria Carmo P
Post Graduate Program in Infectious Diseases and Tropical Medicine, School of Medicine, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Laboratory of Cell-Cell Interactions, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil.
Front Cardiovasc Med. 2021 Feb 3;7:604826. doi: 10.3389/fcvm.2020.604826. eCollection 2020.
Mitral stenosis (MS) is a consequence of rheumatic heart disease that leads to heart failure requiring mechanical intervention. Percutaneous mitral commissurotomy (PMC) is the treatment of choice for the intervention, and currently there are no soluble markers associated with hemodynamic improvement after PMC. This study aims to determine the changes in cytokine/chemokine plasma levels, as well as T cell activation after PMC, and to investigate their association with immediate hemodynamic improvement and clinical outcomes. Plasma samples from eighteen patients with well-defined MS who underwent PMC and 12 healthy controls were analyzed using BioPlex immunoassay. We observed that 16 out of the 27 (60%) molecules assessed were altered in patients' plasma pre-PMC as compared to control group. Of those, IL-1β, IL-12, IL-6, IL-4, PDGF, and CCL11 showed significant decrease after PMC. Stratifying the patients according to adverse outcome after a 28-month median follow up, we detected a significant reduction of IL-1β, IL-12, IL-6, IL-4, IFN-γ, CXCL-10, VEGF, FGF and PDGF post-PMC in patients without events, but not in those who presented adverse events during the follow-up. Patients with adverse outcomes had lower IL-10 pre-PMC, as compared to the ones without adverse events. In addition, the frequency of CD8+ activated memory cells was increased after PMC, while the frequency of CD4+ activated memory cells did not change. Our results show an association between the decrease of specific cytokines and changes in T cell activation with hemodynamic improvement post-PMC, as well as with long-term outcomes, suggesting their possible use as soluble markers for hemodynamic recovery after MS intervention.
二尖瓣狭窄（MS）是风湿性心脏病的后果，可导致心力衰竭，需要进行机械干预。经皮二尖瓣交界切开术（PMC）是该干预措施的首选治疗方法，目前尚无与PMC后血流动力学改善相关的可溶性标志物。本研究旨在确定PMC后细胞因子/趋化因子血浆水平的变化以及T细胞活化情况，并研究它们与即时血流动力学改善和临床结局的关联。使用BioPlex免疫测定法分析了18例接受PMC的明确MS患者和12例健康对照者的血浆样本。我们观察到，与对照组相比，在PMC前患者血浆中评估的27种分子中有16种（60%）发生了改变。其中，IL-1β、IL-12、IL-6、IL-4、血小板衍生生长因子（PDGF）和CCL11在PMC后显著降低。根据28个月的中位随访后的不良结局对患者进行分层，我们发现在无事件发生的患者中，PMC后IL-1β、IL-12、IL-6、IL-4、干扰素-γ（IFN-γ）、CXCL-10、血管内皮生长因子（VEGF）、成纤维细胞生长因子（FGF）和PDGF显著降低，但在随访期间出现不良事件的患者中则没有。与无不良事件的患者相比，有不良结局的患者在PMC前IL-10水平较低。此外，PMC后CD8+活化记忆细胞的频率增加，而CD4+活化记忆细胞的频率没有变化。我们的结果表明，特定细胞因子的降低以及T细胞活化的变化与PMC后血流动力学改善以及长期结局之间存在关联，提示它们可能作为MS干预后血流动力学恢复的可溶性标志物。
